Adjunctive tirofiban fails to reduce 30-day ischemic events in NSTE-ACS patients with complex coronary lesions after PCI: a retrospective cohort study

Adjunctive tirofiban fails to reduce 30-day ischemic events in NSTE-ACS patients with complex coronary lesions after PCI: a retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Adjunctive tirofiban fails to reduce 30-day ischemic events in NSTE-ACS patients with complex coronary lesions after PCI: a retrospective cohort study Ru Sun, Ling Zhou, Jia Cheng, Chen Chen, Jiangtao Yan, Chunxia Zhao, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6313276/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Preventing ischemic events is a critical concern for patients undergoing percutaneous coronary intervention (PCI). Glycoprotein IIb/IIIa inhibitors can significantly reduce short-term ischemic risk in ST-segment elevation myocardial infarction patients after PCI. However, their effectiveness in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients with complex lesions remains unclear. Methods This retrospective study included 1240 NSTE-ACS patients with complex coronary lesions. Patients receiving dual antiplatelet therapy (DAPT) after PCI, with or without tirofiban, were compared. The efficacy endpoint was a composite of 30-day ischemic events, while the safety endpoint was any occurrence of bleeding. Results The addition of tirofiban did not improve the 30-day ischemic outcomes among NSTE-ACS patients with complex lesions, and no significant enhancement was observed in these outcomes following multivariate adjustment (9.1% vs. 8.6%, P = 0.745; adjusted HR: 1.219, P = 0.342). The subgroup analyses showed consistent results. Although additional tirofiban treatment did not increase bleeding risk (3.8% vs. 3.4%, P = 0.742), the medicine costs in the tirofiban group were significantly higher than those in the control group (¥2121 vs. ¥1579, P < 0.001). Conclusions NSTE-ACS patients with complex lesions undergoing PCI may not benefit from additional tirofiban. However, the use of tirofiban significantly increased the medicine costs. The use of DAPT provides adequate antithrombotic protection in NSTE-ACS patients with complex lesions after PCI. NSTE-ACS complex lesion glycoprotein IIb/IIIa inhibitors antiplatelet therapy antithrombotic therapy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Globally, more than 7 million people experience acute coronary syndrome (ACS), of whom approximately 70% have non-ST-segment elevation (NSTE-ACS) [ 1 , 2 ]. Percutaneous coronary intervention (PCI) significantly improves the clinical outcomes of NSTE-ACS patients [ 3 ]. However, stent thrombosis after PCI is a clinical concern that should not be ignored. Increasing clinical evidence has suggested that intensive antithrombotic therapy in NSTE-ACS patients may reduce the incidence of ischemic complications [ 4 ]. Glycoprotein IIb/IIIa inhibitors (GPIs), including abciximab, eptifibatide, and tirofiban, are highly effective antiplatelet agents [ 5 ]. Based on a meta-analysis of 31,402 NSTE-ACS patients, GPI reduced the combined risk of death or myocardial infarction by 9% within 30 days [ 6 ]. Nevertheless, it is important to note that these data were collected before the widespread adoption of P2Y 12 inhibitors. Currently, the combination of aspirin and P2Y 12 inhibitors is recommended as first-line antiplatelet therapy in the latest guidelines, and the effectiveness and safety of GPIs urgently require reevaluation. In NSTE-ACS patients with GPI, the ISAR-REACT 2 trial demonstrated a 25% reduction in 30-day mortality [ 7 ]. However, a large retrospective study involving one million people revealed that GPI do not reduce in-hospital mortality in NSTE-ACS patients who have undergone PCI [ 8 ]. In another retrospective study, GPI failed to improve survival or reduce long-term major adverse cardiovascular events [ 9 ]. Although the role of GPI has been a topic of considerable debate in the aforementioned studies, it is worth noting that these prospective or retrospective studies did not classify the type of lesions or the burden of atherosclerosis in NSTE-ACS patients. Patients with complex coronary artery lesions, including bifurcation lesions, calcified lesions, left main lesions, and chronic total occlusion, have an increased risk of stent thrombosis after PCI [ 10 , 11 ]. Current research aims to reduce the occurrence of ischemic events and improve clinical outcomes by modifying revascularization strategies, selecting different stent types, and utilizing intravascular imaging [ 12 ]. However, few studies have focused on whether intensive antiplatelet strategies, such as the addition of GPI to dual antiplatelet therapy (DAPT), can effectively reduce ischemic complications in NSTE-ACS patients with complex lesions. Because of the associated risk of bleeding, the current global guidelines recommend GPI primarily for cases requiring high-intensity antithrombotic therapy, such as those with a significant thrombus burden or instances of no-reflow and slow flow [ 3 ]. Consequently, the potential for additional GPI to reduce ischemic complications in NSTE-ACS patients with complex lesions who have undergone PCI remains unexplored. To address this gap, we conducted a retrospective study to evaluate the impact of additional tirofiban on short-term outcomes in NSTE-ACS patients with complex lesions using the coronary heart disease (CHD) registry cohort at our hospital. Our aim was to assess ischemic complications and bleeding events within 30 days following PCI in NSTE-ACS patients with complex lesions treated with intensive antiplatelet therapy, with the goal of identifying a more effective antithrombotic strategy. Methods This study was approved by the ethics Review Committee of Tongji Hospital (TJ-IRB202407077). This study adhered to the guidelines set forth in the Declaration of Helsinki. Study design and participants This retrospective study was conducted using an observational cohort of patients who underwent coronary angiography at Tongji Hospital in Wuhan. The cohort was a population-representative CHD cohort with hospitalization data covering central China. The patients included in this study were hospitalized between January 2018 and November 2023. During the study period, 26,506 patients underwent coronary angiography. The inclusion criteria of the present study were as follows: 1) the enrolled patients were diagnosed with NSTE-ACS based on the universal definition of the ESC guidelines in 2023; 2) all patients had complex lesions of the coronary artery and were implanted with at least one stent. Complex lesions included lesions with at least one of the following characteristics: left main coronary artery lesion, occlusion, bifurcation lesion, ostial lesion, lesion length > 20 mm, or calcified lesion. 3) None of the patients had previously received antiplatelet or anticoagulant therapy. The exclusion criteria were non-CHD patients, ST-segment elevation myocardial infarction (STEMI) patients, those who had undergone coronary artery bypass grafting, dialysis patients, long-term antiplatelet drug users, those with no stent implantation, those without complex lesions, and patients with definite thrombus. In total, 1,240 patients were enrolled in this study. Standard antiplatelet therapy included pretreatment with aspirin at a dose of 300 mg, combined with either clopidogrel (300 mg) or ticagrelor (180 mg). Maintenance therapy involved 100 mg of aspirin daily, along with either 75 mg of clopidogrel daily or 180 mg of ticagrelor daily. The decision to use intravenous GP IIb/IIIa inhibitors was made by the operator, with tirofiban being utilized at this hospital. Tirofiban was administered intravenously at an initial dose of 15 µg/kg for 3 minutes, followed by an intravenous infusion at 0.10 µg/kg/min for 24 hours. Based on whether tirofiban was used after PCI, all participants were divided into tirofiban and control groups. Patient characteristics and clinical endpoints The clinical characteristics of the cohort included demographic information (age and sex), comorbidities (diabetes mellitus, hypertension, heart failure, tumors, and hyperlipidemia), laboratory data, left ventricular ejection fraction (LVEF), concomitant medication (ACEI/ARB, beta-blockers, and statins), angiographic and procedural characteristics (target vessel, complex lesions, type of intervention, procedural characteristics, and intravascular imaging), hospital length of stay (LOS), and medicine costs. The efficacy endpoint was a composite of events associated with ischemic conditions within 30 days, which included death, nonfatal myocardial infarction, nonfatal stroke, unstable angina, and acute heart failure. The safety endpoint was any bleeding event, including both major and minor bleeding events. Major and minor bleeding events were classified using the Thrombolysis in Myocardial Infarction criteria. Any event involving bleeding was considered as a bleeding outcome. Major bleeding is defined as an occurrence of intracranial hemorrhage or significant clinical signs of hemorrhage associated with a hemoglobin decline of ≥ 5 g/dL or a hematocrit drop of ≥ 15%. Minor bleeding is defined as clinically significant hemorrhagic indicators with a hemoglobin decrease ranging from 3 to less than 5 g/dL or an absolute hematocrit drop of 9 to less than 15%, as well as any bleeding requiring medical intervention but not meeting the criteria for major bleeding. Thrombocytopenia refers to a platelet count below 100,000 cells/µL or a reduction of 50% or more from the baseline level. Statistical analysis The Shapiro–Wilk test assessed the distribution of continuous data. Continuous variables that followed a normal distribution are presented as mean ± SD, whereas those that were not normally distributed are summarized as medians alongside interquartile ranges (Q1–Q3). For normally distributed measurement data, the student's t–test was applied, while the Mann–Whitney U test was utilized for measurement data that lacked normality. Categorical variables are represented as counts and percentages, with comparisons conducted via the χ 2 test or Fisher's exact test. Multiple imputations were used to handle missing values. To address selection bias and control for confounding variables, propensity score matching was conducted. The propensity score was calculated for each patient in the study cohort by incorporating factors, such as age, sex, BMI, history of diabetes, history of hypertension, and smoking status. Subsequently, patients who received tirofiban were matched with those for whom tirofiban was not indicated, using their propensity scores. Survival curves were created using the Kaplan–Meier method to assess the cumulative likelihood of experiencing ischemic events. Adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated through multivariate Cox proportional hazards regression analysis. The covariates included in the adjusted model were age, sex, LVEF, P2Y 12 receptor antagonists, bifurcation lesions, occlusive lesions, lesion length > 20 mm, number of stents, and IVUS/OCT. The log (− log) survival curves were analyzed to assess the proportional hazards assumption. Stratified analyses were conducted to examine the relationship between tirofiban use and clinical ischemic outcomes across specific subgroups. Subgroup analyses were performed for age, sex, clinical presentation, diabetes, smoking, LVEF, estimated glomerular filtration rate (eGFR), P2Y 12 receptor antagonists, complex lesions, number of stents, IVUS/OCT, and concomitant medications. The results are presented as forest plots. R software (version 4.2.2) was used for both propensity score matching and subgroup analyses, while SPSS software (version 21.0) was employed for the remaining statistical analyses. Results Patient population From January 2018 to November 2023, 3,091 patients diagnosed with NSTE-ACS were identified from a cohort of patients registered at Tongji Hospital who underwent coronary angiography. After excluding 784 previous antiplatelet users, 334 without stent implantation, 487 with non-complex lesions, and 24 with definite thrombi, 1,462 patients constituted the analytic cohort for our study. The tirofiban group comprised 1,016 patients, while the control group consisted of 446 patients who did not receive tirofiban. Prior to matching, various patient characteristics varied between the groups. Those administered tirofiban tended to be younger (61.34 vs 63.15, standardized mean difference [SMD] = 0.183), had a higher likelihood of being a smoker (28.4% vs. 23.3%, SMD = -0.121), displayed an increased rate of non-ST-segment elevation myocardial infarction (NSTEMI) (27.0% vs. 18.6%, SMD = -0.215), and a greater proportion used ticagrelor (32.0% vs. 23.8%, SMD = -0.175). Following a 2:1 propensity score-matching process, the tirofiban and control groups consisted of 798 and 442 patients, respectively. The baseline characteristics of both groups were comparable, with SMDs not exceeding 10% across all variables (0.0-0.1). (Table 1 and Fig. 1 ). Table 1 Baseline clinical characteristics before and after propensity score matching Variables Level Before matching After matching Tirofiban group Control group SMD △ Tirofiban group Control group SMD △ n 1016 446 798 442 Age, y 61.34 (9.95) 63.15 (9.98) 0.183 62.32 (9.71) 63.02 (9.80) 0.029 Sex (%) Male 678 (66.7) 302 (67.7) 0.021 536 (67.2) 298 (67.4) -0.015 Female 338 (33.3) 144 (32.3) -0.021 262 (32.8) 144 (32.6) 0.015 BMI, kg/m 2 24.40 (3.40) 24.28 (3.36) -0.035 24.35 (3.43) 24.27 (3.33) -0.011 Smoking (%) Yes 289 (28.4) 104 (23.3) -0.121 203 (25.4) 104 (23.5) -0.003 No 727 (71.6) 342 (76.7) 0.121 595 (74.6) 338 (76.5) 0.003 Diabetes mellitus (%) Yes 273 (26.9) 125 (28.0) 0.026 218 (27.3) 125 (28.3) 0.023 No 743 (73.1) 321 (72.0) -0.026 580 (72.7) 317 (71.7) -0.023 Hypertension (%) Yes 623 (61.3) 285 (63.9) 0.054 498 (62.4) 281 (63.6) 0.016 No 393 (38.7) 161 (36.1) -0.054 300 (37.6) 161 (36.4) -0.016 Hyperlipidemia (%) Yes 311 (30.6) 125 (28.0) -0.058 233 (29.2) 125 (28.3) 0.005 No 705 (69.4) 321 (72.0) 0.058 565 (70.8) 317 (71.7) -0.005 Heart failure (%) Yes 14 (1.4) 8 (1.8) 0.031 13 (1.6) 7 (1.6) 0.017 No 1002 (98.6) 438 (98.2) -0.031 785 (98.4) 435 (98.4) -0.017 Tumors (%) Yes 30 (3.0) 17 (3.8) 0.045 24 (3.0) 16 (3.6) 0.018 No 986 (97.0) 429 (96.2) -0.045 774 (97.0) 426 (96.4) -0,018 NSTEMI (%) Yes 274 (27.0) 83 (18.6) -0.215 161 (20.2) 83 (18.8) 0.009 No 742 (73.0) 363 (81.4) 0.215 637 (79.8) 359 (81.2) -0.009 UA (%) Yes 742 (73.0) 363 (81.4) 0.215 637 (79.8) 359 (81.2) -0.009 No 274 (27.0) 83 (18.6) -0.215 161 (20.2) 83 (18.8) 0.009 P2Y12 receptor antagonists (%) Clopidogrel 691 (68.0) 340 (76.2) 0.175 592 (74.2) 336 (76.0) -0.046 Ticagrelor 325 (32.0) 106 (23.8) -0.175 206 (25.8) 106 (24.0) 0.046 BMI = body mass index; GPI = glycoprotein IIb/IIIa inhibitor; NSTEMI = non-ST-segment elevation myocardial infarction; SMD = standardized mean difference; UA = unstable angina; n = number of people. STEMI = ST-segment elevation myocardial infarction; CHD = coronary heart disease; CABG = coronary artery bypass grafting; NSTE-ACS = non-ST-segment elevation acute coronary syndrome; PCI = percutaneous coronary intervention; N = number of people Hospitalization examination and concomitant medication Examination data and concomitant medications are presented in Table 2 . Compared to those of the control group, the tirofiban group had a higher red blood cell count (4.44 vs 4.33, P = 0.003), hemoglobin concentration (136 vs. 133, P = 0.029), and LVEF (61% vs. 60%, P = 0.001). Table 2 Hospitalization examination and concomitant medication Tirofiban Group (n = 798) Control Group (n = 442) P value Laboratory data, median (Q1–Q3) or mean ± SD WBC, ×10 9 /L 6.46 (5.38–7.74) 6.37 (5.30–7.58) 0.250 RBC, ×10 12 /L 4.44 (4.05–4.80) 4.33 (3.98–4.72) 0.003 Hb, g/L 136 (124–146) 133 (123–144) 0.029 PLT, ×10 9 /L 210 (173–252) 214 (185–253) 0.141 eGFR, ml/min/1.73 m 2 85.55 (70.60–94.90) 85.10 (70.95–95.10) 0.695 hs-CRP, pg/ml 2.88 (1.00-11.05) 2.36 (0.90–8.92) 0.070 TC, mmol/L 4.42 (3.69–5.09) 4.34 (3.64–4.95) 0.314 LDL, mmol/L 2.73 (2.12–3.42) 2.76 (2.13–3.33) 0.890 Lp(a), mmol/L 41.21(17.07–77.39) 33.61(13.50-72.73) 0.107 K + , mmol/L 4.04 (3.83–4.26) 4.02 (3.77–4.27) 0.419 hs-cTnI, pg/mL 65 (26–292) 58 (24–253) 0.323 Left Ventricular Ejection Fraction, median (Q1–Q3) LVEF (%) 61 (55–65) 60 (51–65) <0.001 Concomitant medication, (no.%) ACEI/ARB 611 (76.6) 337 (76.2) 0.898 Beta-blocker 566 (70.9) 331 (74.9) 0.135 Statins 791 (99.1) 440 (99.5) 0.399 eGFR = estimated glomerular filtration rate; WBC = white blood cell; RBC = red blood cell; Hb = hemoglobin; PLT = platelet; TC = total cholesterol; LDL = low-density lipoprotein; Lp(a) = lipoprotein (a); K + = potassium; hs-CRP = highly sensitive C reaction protein; hs-cTnI = highly sensitive cardiac troponin I; LVEF = left ventricular ejection fraction; ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker. Angiographic and procedural characteristics Analysis of angiographic and procedural characteristics is presented in Table 3 . Patients with bifurcation (15.5% vs. 10.9%, P = 0.022) and occlusion lesions (17.8% vs. 11.1%, P = 0.002) were more often treated with tirofiban, whereas those with long lesions were less frequently treated (92.4% vs. 95.5%, P = 0.033). Tirofiban was also more likely to be used in patients with a higher number of stent implantations (1–3 vs 1–2, P < 0.001) and in those who underwent intravascular imaging (6.4% vs. 3.2%, P = 0.015). The prevalence of complex lesion components within the groups is shown in Fig. 2 . Table 3 Angiographic and procedural characteristics Tirofiban Group (n = 798) Control Group (n = 442) P value Target vessel, (no.%) Left main artery 27 (3.4) 7 (1.6) 0.063 Left anterior descending artery 538 (67.4) 287 (64.9) 0.374 Left circumflex artery 230 (28.8) 126 (28.5) 0.906 Right coronary artery 219 (27.4) 112 (25.3) 0.422 1-vessel 612 (76.7) 360 (81.4) 0.051 2-vessel 179 (22.4) 81 (18.3) 0.089 3-vessel 7 (0.9) 1 (0.2) 0.170 Complex lesions, (no.%) Left main artery lesion 27 (3.4) 7 (1.6) 0.063 ≥ 1 bifurcation lesion 124 (15.5) 48 (10.9) 0.022 ≥ 1 ostial lesion 44 (5.5) 22 (5.0) 0.687 ≥ 1 occlusion 142 (17.8) 49 (11.1) 0.002 ≥ 1 lesion ≥ 20 mm 737 (92.4) 422 (95.5) 0.033 ≥ 1 calcified lesion 40 (5.0) 32 (7.2) 0.108 Type of intervention, (no.%) Drug-eluting stent 798 (100) 442 (100) 1.000 Procedural characteristics, (no.%) / median (Q1–Q3) Number of stents implanted 2 (1–3) 2 (1–2) <0.001 Stent length 25 (22–29) 25 (23–29) 0.473 Stent diameter 2.87 (2.75–3.12) 2.91 (2.67–3.13) 0.841 Intravascular imaging, (no.%) IVUS/OCT 51 (6.4) 14 (3.2) 0.015 IVUS = intravascular ultrasound; OCT = optical coherence tomography; n = number of people. Complex coronary lesions were defined as those meeting at least one of the following criteria: left main coronary artery lesion, occlusion, bifurcation lesion, ostial lesion, lesion length > 20 mm, or a calcified lesion. This figure illustrates the distribution of these lesion types across study groups. Notably, lesions > 20 mm in length were the most common, while left main coronary artery lesions were the least prevalent in both groups. Hospital length of stay and medicine costs LOS and medicine costs are depicted in Fig. 3 . There was no significant difference in LOS between the tirofiban and control groups (5.10 vs 5.11, P = 0.555). However, the medicine costs in the tirofiban group were significantly higher than those in the control group (¥2121 vs. ¥1579, P < 0.001). ns = no significance; ***= P < 0.001. Clinical outcomes The unadjusted and multivariate-adjusted ischemia outcomes during the 30 days after PCI are shown in Table 4 and Fig. 4 . In the tirofiban group, nine patients died compared to two patients in the control group (1.1% vs. 0.5%, P = 0.369; adjusted HR: 4.369, P = 0.177). Additionally, 11 and six patients in the tirofiban and control groups, respectively, experienced either nonfatal myocardial infarction or nonfatal cerebral infarction (1.4% vs. 1.4%, P = 0.976; adjusted HR: 1.160, P = 0.782). Unstable angina was recorded in 53 individuals in the tirofiban cohort compared to 30 individuals in the control cohort (6.6% vs. 6.8%, P = 0.922; adjusted HR: 1.018, P = 0.941). Acute heart failure was observed in two individuals in the tirofiban cohort, while five individuals in the control cohort experienced this condition (0.6% vs. 1.1%, P = 0.113; adjusted HR: 0.148, P = 0.083). In terms of composite ischemia, 73 patients in the tirofiban cohort and 38 patients in the control cohort were affected (9.1% vs. 8.6%, P = 0.745; adjusted HR: 1.219, P = 0.342). In summary, there was no statistically significant difference in the 30-day efficacy endpoints between the different tirofiban groups. Bleeding outcomes are presented in Table 4 . Major bleeding events were observed in four patients in the tirofiban group compared with two patients in the control group (0.5% vs. 0.5%, P = 0.906). Minor bleeding was reported in 26 patients in the tirofiban cohort and 13 individuals in the control cohort (3.3% vs. 2.9%, P = 0.759). Major or minor bleeding was documented in 30 patients in the tirofiban group and 15 patients in the control group (3.8% vs. 3.4%, P = 0.742). Overall, there were no statistically significant differences in the safety endpoints between the two groups. Table 4 Clinical outcomes Tirofiban Group (n = 798) Control Group (n = 442) P value Clinical ischemic outcomes, (no.%) Composite ischemia (all-cause death, nonfatal myocardial infarction, nonfatal cerebral infraction, unstable angina, acute heart failure) 73 (9.1) 38 (8.6) 0.745 All-cause death 9 (1.1) 2 (0.5) 0.369 Nonfatal myocardial infarction, nonfatal cerebral infraction 11 (1.4) 6 (1.4) 0.976 Unstable angina 53 (6.6) 30 (6.8) 0.922 Acute heart failure 2 (0.6) 5 (1.1) 0.113 Clinical bleeding outcomes, (no.%) Any bleeding 30 (3.8) 15 (3.4) 0.742 Major bleeding 4 (0.5) 2 (0.5) 0.906 Minor bleeding 26 (3.3) 13 (2.9) 0.759 GPI = glycoprotein IIb/IIIa inhibitor; n = number of people. A, 30-day all-cause mortality in the tirofiban group versus control group; B, 30-day incidence of unstable angina in the tirofiban group versus control group; C, 30-day incidence of nonfatal myocardial infarction plus nonfatal cerebral infarction in the tirofiban group versus control group; D, 30-day incidence of acute heart failure in the tirofiban group versus control group. E, 30-day composite ischemic events (all-cause death, unstable angina, nonfatal cerebral infarction, acute heart failure, and nonfatal myocardial infarction) in the tirofiban group versus control group. A-E Adjusted for age, sex, LVEF, P2Y12 receptor antagonists, bifurcation lesions, occlusive lesions, lesion length > 20 mm, number of stents, and intravascular ultrasound/optical coherence tomography. Multivariate Cox proportional hazard regression analysis was used to determine adjusted hazard ratios (HR) and 95% confidence intervals (CI). Subgroup analyses Subgroup analysis revealed no significant difference in mortality between the control and tirofiban groups in the overall population (adjusted HR: 1.10, P = 0.619). Subgroup analyses stratified by age, sex, clinical presentation, presence of diabetes mellitus, LVEF, eGFR, P2Y 12 receptor inhibitors, and other lesion characteristics consistently demonstrated no significant interaction effects (all P > 0.05) (Fig. 5 ). A dot-whisker plot showing the association between GPI use and 30-day composite ischemic events (all-cause death, unstable angina, nonfatal cerebral infarction, acute heart failure, and nonfatal myocardial infarction). Hazard ratio adjusted for sex, age, P2Y12 inhibitors, and clinical presentation. UA = unstable angina; NSTEMI = non-ST-segment elevation myocardial infarction; eGFR = estimated glomerular filtration rate; LVEF = left ventricular ejection fraction; IVUS = intravascular ultrasonography; OCT = optical coherence tomography; ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; CI = confidence interval; OR = odds ratio. Discussion In this study, we evaluated whether an intensive antiplatelet regimen combining tirofiban with DAPT could reduce the occurrence of ischemic complications in NSTE-ACS patients with complex lesions undergoing PCI. The results showed that additional administration of tirofiban did not provide any significant clinical benefit for ischemic events within 30 days post-procedure. This is the first case-matched study to evaluate the effect of tirofiban in addition to DAPT on the clinical prognosis of NSTE-ACS patients with complex lesions. In previous studies, all patients who underwent PCI were enrolled regardless of the anatomical features of the target lesion. Therefore, patients with complex and non-complex lesions accounted for a certain proportion. However, our study focused exclusively on a population with complex target vessel lesions at high risk of thrombosis, making the subjects more distinctive. Earlier trials assessed the effects of GPI prior to the routine use of P2Y 12 receptor antagonists. A meta-analysis involving six trials encompassing 29,570 participants, among which 6,637 received revascularization, demonstrated a notable decrease in the incidence of death or myocardial infarction within 30 days in NSTE-ACS patients [ 13 ]. However, no statistical significance was observed in any of the individual studies. The trials included in this analysis were PRISM, PARAGON B, PARAGON A, PURSUIT, GUSTO IV, and PRISM-PLUS [ 14 – 19 ]. In these studies, patients were treated with both aspirin and GPI, whereas all participants in our study were administered a loading dose of a P2Y 12 receptor blocker. A previous study confirmed that P2Y 12 receptors play a major role in the amplification of platelet activation and that the combination of a P2Y 12 receptor antagonist and aspirin has an additive effect on the inhibition of platelet activation and related platelet responses [ 20 ]. As GPI are known to significantly inhibit the common final pathway of platelet aggregation by blocking the GP IIb/IIIa receptor [ 21 ], more than two-thirds of NSTE-ACS patients with complex lesions in this study were empirically treated with tirofiban by the operator to reduce the risk of thrombotic events. However, our results showed that tirofiban did not provide any additional benefits in preventing thrombotic events after PCI. We believe that one of the limitations of tirofiban is that its additional antiplatelet advantage is reduced when combined with aspirin and a P2Y 12 receptor antagonist. Another possible factor is its short half-life. In the era of DAPT, the effects of GPI are controversial. The On-TIME 2 trial involved STEMI patients who underwent PCI with a loading dose of 500 mg aspirin and 600 mg clopidogrel [ 22 ]. The clinical results of this study demonstrated better 30-day outcomes with GPI than with placebo, primarily driven by a reduction in thrombotic bailout, without an increased risk of bleeding [ 22 ]. In addition, the ISAR-REACT 2 trial, involving 2,022 high-risk NSTE-ACS patients, showed that GPI reduced 30-day ischemic events, exceeding expectations [ 7 ]. However, in the subgroup analysis of NSTEMI and UA patients, improvements in mortality and ischemic outcomes were observed only in NSTEMI patients, with no difference noted in UA patients [ 7 ]. In the ISAR-REACT 2 trial, approximately 50% of the patients were NSTEMI, whereas only about 20% of the patients in our study were NSTEMI after propensity matching. NSTEMI patients are more prone to plaque rupture and, consequently, have a higher risk of thrombosis. This makes them more likely to benefit from GPI treatment owing to its anti-inflammatory and antithrombotic properties. However, compared with those in previous studies [ 7 ], our subgroup analyses did not yield similar results. The discrepancies may be attributed to differences in the study populations, especially the significant variation in the proportion of NSTEMI patients. To address the issue of insufficient evidence, further confirmatory trials involving NSTEMI and UA patients receiving DAPT, or even a potent DAPT strategy, may be needed to enhance the statistical power of subgroup analysis results from previous studies. Few studies have been conducted to characterize complex coronary lesions, despite the increased risk of ischemic complications and the challenges of complex PCI procedures. This gap is largely owing to the lack of standardization criteria and definitions for complex coronary lesions [ 23 , 24 ]. The definition of complex coronary anatomical lesions in most earlier studies was based on the 1988 AHA guidelines for type B2 and C lesions. Therefore, the definition of complex lesions in our study was derived from these previous studies [ 25 ]. In the ISAR-REACT trial, which included stable coronary artery disease patients undergoing PCI, subgroup analysis revealed that GPI did not lead to a decrease in 30-day mortality or cardiac events among patients with complex lesions [ 26 ]. Another retrospective study indirectly assessed the role of GPI, finding no significant difference in the 30-day occurrence of major adverse events between NSTE-ACS patients treated with unfractionated heparin combined with GPI and those treated with bivalirudin after complex PCI [ 27 ]. The patients in both studies received adequate doses of aspirin and P2Y 12 inhibitors. In our study, patients with more complex lesions or those who had more stents implanted used GPI more frequently. However, the additional use of GPI did not reduce 30-day ischemic events. These findings provide preliminary evidence for the anti-ischemic efficacy of DAPT, even in the absence of GPIs, in patients with complex lesions. These results indicate that dual antiplatelet strategies can be used in accordance with the guidelines for NSTE-ACS patients with complex lesions. However, GPI are used exclusively in cases with a significant thrombus burden; however, their use, which often depends on the intervenor’s experience, requires further standardization. Limitations Firstly, this was a single-center, continuous, retrospective observational study. Owing to the nature of observational studies, the results may be affected by confounding factors. Nonetheless, we used propensity score matching for major clinical variables to adjust for confounding factors, and multivariate adjustment for outcomes was performed to support our findings. Secondly, the sample size was small. We excluded patients who had previously received antiplatelet therapy and retained only those who were first-time antiplatelet users to ensure equal onset and timing of DAPT in the study population. Finally, our results may not be generalizable to patients treated with other GP IIb/IIIa inhibitors such as abciximab and eptifibatide, because the patients in this study were treated with tirofiban alone. Conclusion In NSTE-ACS patients with complex lesions, additional tirofiban use did not improve short-term mortality and ischemic clinical outcomes but significantly increased drug costs. Abbreviations ACS acute coronary syndrome CHD coronary heart disease DAPT dual antiplatelet therapy GPI glycoprotein IIb/IIIa inhibitor NSTE-ACS non-ST-segment elevation acute coronary syndrome NSTEMI non-ST-segment elevation myocardial infarction PCI percutaneous coronary intervention STEMI ST-segment elevation myocardial infarction UA unstable angina Declarations Funding This study was conducted without external financial support. All aspects of the research, including design, data handling, analysis, and manuscript preparation, were independently managed by the authors. Author information Authors and Affiliations Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China Ru Sun, Ling Zhou, Jia Cheng, Chen Chen, Jiangtao Yan, Chunxia Zhao & Feng Wang Authors' contributions All authors contributed to the study conception and design. RS, FW, and CZ conceived the research topic and framework. RS, LZ, and JC conducted data cleaning and analysis for the cohort study. CC and JY completed the statistical analysis. RS, LZ, and JC drafted the manuscript. FW, CC, and CZ reviewed the data and revised the manuscript. All authors read and approved the final manuscript. Corresponding author Correspondence to Feng Wang. Ethics approval This research adhered to the ethical standards established by the 1964 Declaration of Helsinki and its subsequent revisions. The institutional review board of Tongji Hospital provided ethical approval for this work (TJ-IRB202407077). All patients signed the informed consent to participate in the study. Consent for publication The authors affirm that patients provided informed consent regarding publishing their data and images. Declarations of competing interests The authors declare no competing interests. Data availability statement The data that support the findings of this study are available from the Health Information Management Department of Tongji Hospital, but restrictions apply to the availability of these data, which were used under institutional data governance protocols for the current study, and thus are not publicly accessible. Data may however be obtained from the corresponding author upon reasonable scientific request and with formal approval from the Ethics Committee of Tongji Hospital. Acknowledgements None. References Reed G, Rossi J, Cannon C. Acute myocardial infarction. Lancet. 2007;389(10065):197–210. Bhatt D, Lopes R, Harrington R. Diagnosis and treatment of acute coronary syndromes: A review. JAMA. 2022;327(7):662–75. Lawton J, Tamis-Holland J, Bangalore S, Bates E, Beckie T, Bischoff J, et al. ACC/AHA/SCAI guideline for coronary artery revascularization: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(2):e21–129. 10.1016/j.jacc.2021.09.006 . Bergmark B, Mathenge N, Merlini P, Lawrence-Wright M, Giugliano R. Acute coronary syndromes. Lancet. 2022;399(10332):1347–58. Starnes H, Patel A, Stouffer G. Optimal use of platelet glycoprotein IIb/IIIa receptor antagonists in patients undergoing percutaneous coronary interventions. Drugs. 2011;71(15):2009–30. Boersma E, Harrington R, Moliterno D, White H, Théroux P, van de Werf F, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: A meta-analysis of all major randomised clinical trials. Lancet. 2002;359(9302):189–98. Kastrati A, Mehilli J, Neumann F, Dotzer F, ten Berg J, Bollwein H, et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: The ISAR-REACT 2 randomized trial. JAMA. 2006;295(13):1531–8. Safley D, Venkitachalam L, Kennedy K, Cohen D. Impact of glycoprotein IIb/IIIa inhibition in contemporary percutaneous coronary intervention for acute coronary syndromes: Insights from the National Cardiovascular Data Registry. JACC Cardiovasc Interv. 2015;8(12):1574–82. Howard J, Jones D, Gallagher S, Rathod K, Antoniou S, Wright P et al. Glycoprotein IIb/IIIa inhibitors use and outcome after percutaneous coronary intervention for non-ST elevation myocardial infarction. Biomed Res Int 2014; 2014:643981. Yadav M, Généreux P, Palmerini T, Caixeta A, Madhavan M, Xu K, et al. SYNTAX score and the risk of stent thrombosis after percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes: An ACUITY trial substudy. Catheter Cardiovasc Interv. 2015;85(1):1–10. Garg S, Sarno G, Girasis C, Vranckx P, de Vries T, Swart M, et al. A patient-level pooled analysis assessing the impact of the SYNTAX (synergy between percutaneous coronary intervention with Taxus and cardiac surgery) score on 1-year clinical outcomes in 6,508 patients enrolled in contemporary coronary stent trials. JACC Cardiovasc Interv. 2011;4(6):645–53. Werner N, Nickenig G, Sinning J. Complex PCI procedures: Challenges for the interventional cardiologist. Clin Res Cardiol. 2018;1107(Suppl 2):64–73. Roffi M, Chew D, Mukherjee D, Bhatt D, White J, Moliterno D, et al. Platelet glycoprotein IIb/IIIa inhibition in acute coronary syndromes: Gradient of benefit related to the revascularization strategy. Eur Heart J. 2002;23(18):1441–8. Simoons ML. Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularization: The GUSTO IV-ACS randomized trial. Lancet. 2001;357(9272):1915–24. PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med. 1998;339:436–43. Moliterno D, PARAGON B International Steering Committee. Patient-specific dosing of IIb/IIIa antagonists during acute coronary syndromes: Rationale and design of the PARAGON B study. Am Heart J. 2000;139(4):563–6. PARAGON Investigators. International, randomized, controlled trial of lamifiban (a platelet glycoprotein IIb/IIIa inhibitor), heparin, or both in unstable angina. Circulation. 1998;97(24):2386–95. PARAGON Investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. N Engl J Med. 1998;338:1488–97. PRISM Study Investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med. 1998;338:1498–505. Capodanno D, Angiolillo D. Personalized antiplatelet therapies for coronary artery disease: what the future holds. Eur Heart J. 2023;44(32):3059–72. Sharifi-Rad J, Sharopov F, Ezzat S, Zam W, Ademiluyi A, Oyeniran O, et al. An updated review on glycoprotein IIb/IIIa inhibitors as antiplatelet agents: Basic and clinical perspectives. High Blood Press Cardiovasc Prev. 2023;30:93–107. Van’t Hof A, Berg J, Heestermans T, Dill T, Funck R, van Werkum W, et al. Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): A multicentre, double-blind, randomized controlled trial. Lancet. 2008;372:537–46. Collet J, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt D, et al. 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021;42:1289–367. Kirtane A, Doshi D, Leon M, Lasala J, Ohman E, O’Neill W, et al. Treatment of higher-risk patients with an indication for revascularization: Evolution within the field of contemporary percutaneous coronary intervention. Circulation. 2016;134:422–31. Ryan T, Faxon D, Gunnar R, Kennedy J, King S 3rd, Loop F, et al. Guidelines for percutaneous transluminal coronary angioplasty: A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Percutaneous Transluminal Coronary Angioplasty). Circulation. 1988;78:486–502. Kastrati A, Mehilli J, Schühlen H, Dirschinger J, Dotzer F, ten Berg J, et al. A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med. 2004;350:232–8. Cortese B, Micheli A, Picchi A, Bandinelli L, Brizi M, Severi S, et al. Safety and efficacy of a prolonged bivalirudin infusion after urgent and complex percutaneous coronary interventions: A descriptive study. Coron Artery Dis. 2009;20:348–53. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6313276","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":453456369,"identity":"053572b7-4154-4f4c-857c-ebc7d85658c2","order_by":0,"name":"Ru Sun","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Ru","middleName":"","lastName":"Sun","suffix":""},{"id":453456370,"identity":"0125effe-e34f-4004-a3b0-2026a647e9b2","order_by":1,"name":"Ling Zhou","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Ling","middleName":"","lastName":"Zhou","suffix":""},{"id":453456371,"identity":"86e6a87a-5d30-4e12-b52b-c32e428df06c","order_by":2,"name":"Jia Cheng","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"Cheng","suffix":""},{"id":453456372,"identity":"e7917691-0b2b-4788-b793-16f9422c855f","order_by":3,"name":"Chen Chen","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Chen","middleName":"","lastName":"Chen","suffix":""},{"id":453456373,"identity":"768211e3-7f42-4512-b649-03e6d4c50d1d","order_by":4,"name":"Jiangtao Yan","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Jiangtao","middleName":"","lastName":"Yan","suffix":""},{"id":453456374,"identity":"1015cc3c-054c-41c7-93d2-3c7abcbc6cb3","order_by":5,"name":"Chunxia Zhao","email":"","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Chunxia","middleName":"","lastName":"Zhao","suffix":""},{"id":453456375,"identity":"a53e3b21-2067-4729-81af-1850f250f446","order_by":6,"name":"Feng Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0UlEQVRIiWNgGAWjYLCCCgYGZgP2xsaHH4jWcobBgNmA53CzsQQpWhgMJNLbBHiIUW1w/OzhFwcY/rCbSz5sY5BgsJPTbSCk5UxemsUBoMMsZye2PShgSDY2O0BAi9mBHDPjDyC/3E5sN5BgOJC4jaCW82/MDEC2GNw82CbBQ5SWGznGD8BabjASqcX+xhszhgMMxswGZxKBgWxAhF8k+3OMPxxgkEs2OH784cMPFXZyBLUAAZsE4z+GZAjbgLByEGAGJRM74tSOglEwCkbBiAQAFzhDw9lz7YcAAAAASUVORK5CYII=","orcid":"","institution":"Huazhong University of Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"Feng","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2025-03-26 14:23:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6313276/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6313276/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82559488,"identity":"a4912607-d927-46e8-afa2-53fc2f715e38","added_by":"auto","created_at":"2025-05-13 01:28:30","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":164494,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6313276/v1/9b53ad35968f76d2d7fe990f.jpeg"},{"id":82559490,"identity":"27648c85-062e-4b6e-94f1-3252cbca9956","added_by":"auto","created_at":"2025-05-13 01:28:30","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":118865,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePrevalence of complex lesion components across groups\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6313276/v1/d1a3137cd1c88f8848b71559.jpeg"},{"id":82559487,"identity":"d1659a34-df02-45ee-9fe3-34ff9a4f62ae","added_by":"auto","created_at":"2025-05-13 01:28:30","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":77109,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHospital length of stay and medicine costs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ens= no significance; ***= \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6313276/v1/11eca9efe98c6d776c5733a5.jpeg"},{"id":82560714,"identity":"bbe0d8c6-1b2a-4d0a-bb09-3083e9e39fca","added_by":"auto","created_at":"2025-05-13 01:36:30","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":174987,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAdjusted Kaplan–Meier curves in tirofiban group vs control group\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6313276/v1/9534b3d71ca91e17cd77b4f9.jpeg"},{"id":82559496,"identity":"1d4358af-574e-4329-9ac4-f6d14074682c","added_by":"auto","created_at":"2025-05-13 01:28:30","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":541815,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSubgroup analysis\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6313276/v1/da5343ee9ff482bc393ce38c.jpeg"},{"id":82562313,"identity":"40dcac3a-f848-4c32-a9b4-0d20f4cd2c6a","added_by":"auto","created_at":"2025-05-13 01:44:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2400024,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6313276/v1/6be51f69-8ca3-432c-aca0-2ffc7d2463f4.pdf"},{"id":82559498,"identity":"9dff4f7a-bcdf-473c-aab0-7bf77c400467","added_by":"auto","created_at":"2025-05-13 01:28:30","extension":"jpeg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":208599,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCentral figure\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6313276/v1/b4c4e7844501bd9d2084a5f1.jpeg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Adjunctive tirofiban fails to reduce 30-day ischemic events in NSTE-ACS patients with complex coronary lesions after PCI: a retrospective cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGlobally, more than 7\u0026nbsp;million people experience acute coronary syndrome (ACS), of whom approximately 70% have non-ST-segment elevation (NSTE-ACS) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Percutaneous coronary intervention (PCI) significantly improves the clinical outcomes of NSTE-ACS patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, stent thrombosis after PCI is a clinical concern that should not be ignored. Increasing clinical evidence has suggested that intensive antithrombotic therapy in NSTE-ACS patients may reduce the incidence of ischemic complications [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Glycoprotein IIb/IIIa inhibitors (GPIs), including abciximab, eptifibatide, and tirofiban, are highly effective antiplatelet agents [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Based on a meta-analysis of 31,402 NSTE-ACS patients, GPI reduced the combined risk of death or myocardial infarction by 9% within 30 days [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Nevertheless, it is important to note that these data were collected before the widespread adoption of P2Y\u003csub\u003e12\u003c/sub\u003e inhibitors. Currently, the combination of aspirin and P2Y\u003csub\u003e12\u003c/sub\u003e inhibitors is recommended as first-line antiplatelet therapy in the latest guidelines, and the effectiveness and safety of GPIs urgently require reevaluation.\u003c/p\u003e \u003cp\u003eIn NSTE-ACS patients with GPI, the ISAR-REACT 2 trial demonstrated a 25% reduction in 30-day mortality [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, a large retrospective study involving one million people revealed that GPI do not reduce in-hospital mortality in NSTE-ACS patients who have undergone PCI [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In another retrospective study, GPI failed to improve survival or reduce long-term major adverse cardiovascular events [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Although the role of GPI has been a topic of considerable debate in the aforementioned studies, it is worth noting that these prospective or retrospective studies did not classify the type of lesions or the burden of atherosclerosis in NSTE-ACS patients.\u003c/p\u003e \u003cp\u003ePatients with complex coronary artery lesions, including bifurcation lesions, calcified lesions, left main lesions, and chronic total occlusion, have an increased risk of stent thrombosis after PCI [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Current research aims to reduce the occurrence of ischemic events and improve clinical outcomes by modifying revascularization strategies, selecting different stent types, and utilizing intravascular imaging [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, few studies have focused on whether intensive antiplatelet strategies, such as the addition of GPI to dual antiplatelet therapy (DAPT), can effectively reduce ischemic complications in NSTE-ACS patients with complex lesions. Because of the associated risk of bleeding, the current global guidelines recommend GPI primarily for cases requiring high-intensity antithrombotic therapy, such as those with a significant thrombus burden or instances of no-reflow and slow flow [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Consequently, the potential for additional GPI to reduce ischemic complications in NSTE-ACS patients with complex lesions who have undergone PCI remains unexplored. To address this gap, we conducted a retrospective study to evaluate the impact of additional tirofiban on short-term outcomes in NSTE-ACS patients with complex lesions using the coronary heart disease (CHD) registry cohort at our hospital. Our aim was to assess ischemic complications and bleeding events within 30 days following PCI in NSTE-ACS patients with complex lesions treated with intensive antiplatelet therapy, with the goal of identifying a more effective antithrombotic strategy.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e This study was approved by the ethics Review Committee of Tongji Hospital (TJ-IRB202407077). This study adhered to the guidelines set forth in the Declaration of Helsinki.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eThis retrospective study was conducted using an observational cohort of patients who underwent coronary angiography at Tongji Hospital in Wuhan. The cohort was a population-representative CHD cohort with hospitalization data covering central China. The patients included in this study were hospitalized between January 2018 and November 2023. During the study period, 26,506 patients underwent coronary angiography. The inclusion criteria of the present study were as follows: 1) the enrolled patients were diagnosed with NSTE-ACS based on the universal definition of the ESC guidelines in 2023; 2) all patients had complex lesions of the coronary artery and were implanted with at least one stent. Complex lesions included lesions with at least one of the following characteristics: left main coronary artery lesion, occlusion, bifurcation lesion, ostial lesion, lesion length\u0026thinsp;\u0026gt;\u0026thinsp;20 mm, or calcified lesion. 3) None of the patients had previously received antiplatelet or anticoagulant therapy. The exclusion criteria were non-CHD patients, ST-segment elevation myocardial infarction (STEMI) patients, those who had undergone coronary artery bypass grafting, dialysis patients, long-term antiplatelet drug users, those with no stent implantation, those without complex lesions, and patients with definite thrombus.\u003c/p\u003e \u003cp\u003eIn total, 1,240 patients were enrolled in this study. Standard antiplatelet therapy included pretreatment with aspirin at a dose of 300 mg, combined with either clopidogrel (300 mg) or ticagrelor (180 mg). Maintenance therapy involved 100 mg of aspirin daily, along with either 75 mg of clopidogrel daily or 180 mg of ticagrelor daily. The decision to use intravenous GP IIb/IIIa inhibitors was made by the operator, with tirofiban being utilized at this hospital. Tirofiban was administered intravenously at an initial dose of 15 \u0026micro;g/kg for 3 minutes, followed by an intravenous infusion at 0.10 \u0026micro;g/kg/min for 24 hours. Based on whether tirofiban was used after PCI, all participants were divided into tirofiban and control groups.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatient characteristics and clinical endpoints\u003c/h3\u003e\n\u003cp\u003eThe clinical characteristics of the cohort included demographic information (age and sex), comorbidities (diabetes mellitus, hypertension, heart failure, tumors, and hyperlipidemia), laboratory data, left ventricular ejection fraction (LVEF), concomitant medication (ACEI/ARB, beta-blockers, and statins), angiographic and procedural characteristics (target vessel, complex lesions, type of intervention, procedural characteristics, and intravascular imaging), hospital length of stay (LOS), and medicine costs.\u003c/p\u003e \u003cp\u003eThe efficacy endpoint was a composite of events associated with ischemic conditions within 30 days, which included death, nonfatal myocardial infarction, nonfatal stroke, unstable angina, and acute heart failure. The safety endpoint was any bleeding event, including both major and minor bleeding events. Major and minor bleeding events were classified using the Thrombolysis in Myocardial Infarction criteria. Any event involving bleeding was considered as a bleeding outcome. Major bleeding is defined as an occurrence of intracranial hemorrhage or significant clinical signs of hemorrhage associated with a hemoglobin decline of \u0026ge;\u0026thinsp;5 g/dL or a hematocrit drop of \u0026ge;\u0026thinsp;15%. Minor bleeding is defined as clinically significant hemorrhagic indicators with a hemoglobin decrease ranging from 3 to less than 5 g/dL or an absolute hematocrit drop of 9 to less than 15%, as well as any bleeding requiring medical intervention but not meeting the criteria for major bleeding. Thrombocytopenia refers to a platelet count below 100,000 cells/\u0026micro;L or a reduction of 50% or more from the baseline level.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe Shapiro\u0026ndash;Wilk test assessed the distribution of continuous data. Continuous variables that followed a normal distribution are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, whereas those that were not normally distributed are summarized as medians alongside interquartile ranges (Q1\u0026ndash;Q3). For normally distributed measurement data, the student's t\u0026ndash;test was applied, while the Mann\u0026ndash;Whitney U test was utilized for measurement data that lacked normality. Categorical variables are represented as counts and percentages, with comparisons conducted via the χ\u003csup\u003e2\u003c/sup\u003e test or Fisher's exact test. Multiple imputations were used to handle missing values. To address selection bias and control for confounding variables, propensity score matching was conducted. The propensity score was calculated for each patient in the study cohort by incorporating factors, such as age, sex, BMI, history of diabetes, history of hypertension, and smoking status. Subsequently, patients who received tirofiban were matched with those for whom tirofiban was not indicated, using their propensity scores. Survival curves were created using the Kaplan\u0026ndash;Meier method to assess the cumulative likelihood of experiencing ischemic events. Adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated through multivariate Cox proportional hazards regression analysis. The covariates included in the adjusted model were age, sex, LVEF, P2Y\u003csub\u003e12\u003c/sub\u003e receptor antagonists, bifurcation lesions, occlusive lesions, lesion length\u0026thinsp;\u0026gt;\u0026thinsp;20 mm, number of stents, and IVUS/OCT. The log (\u0026minus;\u0026thinsp;log) survival curves were analyzed to assess the proportional hazards assumption.\u003c/p\u003e \u003cp\u003eStratified analyses were conducted to examine the relationship between tirofiban use and clinical ischemic outcomes across specific subgroups. Subgroup analyses were performed for age, sex, clinical presentation, diabetes, smoking, LVEF, estimated glomerular filtration rate (eGFR), P2Y\u003csub\u003e12\u003c/sub\u003e receptor antagonists, complex lesions, number of stents, IVUS/OCT, and concomitant medications. The results are presented as forest plots. R software (version 4.2.2) was used for both propensity score matching and subgroup analyses, while SPSS software (version 21.0) was employed for the remaining statistical analyses.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003ePatient population\u003c/h2\u003e \u003cp\u003eFrom January 2018 to November 2023, 3,091 patients diagnosed with NSTE-ACS were identified from a cohort of patients registered at Tongji Hospital who underwent coronary angiography. After excluding 784 previous antiplatelet users, 334 without stent implantation, 487 with non-complex lesions, and 24 with definite thrombi, 1,462 patients constituted the analytic cohort for our study. The tirofiban group comprised 1,016 patients, while the control group consisted of 446 patients who did not receive tirofiban. Prior to matching, various patient characteristics varied between the groups. Those administered tirofiban tended to be younger (61.34 vs 63.15, standardized mean difference [SMD]\u0026thinsp;=\u0026thinsp;0.183), had a higher likelihood of being a smoker (28.4% vs. 23.3%, SMD = -0.121), displayed an increased rate of non-ST-segment elevation myocardial infarction (NSTEMI) (27.0% vs. 18.6%, SMD = -0.215), and a greater proportion used ticagrelor (32.0% vs. 23.8%, SMD = -0.175). Following a 2:1 propensity score-matching process, the tirofiban and control groups consisted of 798 and 442 patients, respectively. The baseline characteristics of both groups were comparable, with SMDs not exceeding 10% across all variables (0.0-0.1). (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline clinical characteristics before and after propensity score matching\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLevel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eBefore matching\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eAfter matching\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTirofiban group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSMD\u003csup\u003e△\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTirofiban group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSMD\u003csup\u003e△\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e446\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e798\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e442\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.34 (9.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.15 (9.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e62.32 (9.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e63.02 (9.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e678 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e302 (67.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e536 (67.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e298 (67.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e338 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e144 (32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e262 (32.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e144 (32.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.40 (3.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.28 (3.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e24.35 (3.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e24.27 (3.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.011\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSmoking (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e289 (28.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e104 (23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e203 (25.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e104 (23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e727 (71.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e342 (76.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e595 (74.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e338 (76.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDiabetes mellitus (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e273 (26.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e125 (28.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e218 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e125 (28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e743 (73.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e321 (72.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e580 (72.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e317 (71.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHypertension (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e623 (61.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e285 (63.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e498 (62.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e281 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e393 (38.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e161 (36.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e300 (37.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e161 (36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHyperlipidemia (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e311 (30.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e125 (28.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e233 (29.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e125 (28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e705 (69.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e321 (72.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e565 (70.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e317 (71.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHeart failure (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e13 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1002 (98.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e438 (98.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e785 (98.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e435 (98.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTumors (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e24 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e986 (97.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e429 (96.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e774 (97.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e426 (96.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0,018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNSTEMI (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e274 (27.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83 (18.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.215\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e161 (20.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e83 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e742 (73.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e363 (81.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.215\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e637 (79.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e359 (81.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eUA (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e742 (73.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e363 (81.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.215\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e637 (79.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e359 (81.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e274 (27.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83 (18.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.215\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e161 (20.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e83 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP2Y12 receptor antagonists (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eClopidogrel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e691 (68.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e340 (76.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.175\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e592 (74.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e336 (76.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.046\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTicagrelor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e325 (32.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e106 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.175\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e206 (25.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e106 (24.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eBMI\u0026thinsp;=\u0026thinsp;body mass index; GPI\u0026thinsp;=\u0026thinsp;glycoprotein IIb/IIIa inhibitor; NSTEMI\u0026thinsp;=\u0026thinsp;non-ST-segment elevation myocardial infarction; SMD\u0026thinsp;=\u0026thinsp;standardized mean difference; UA\u0026thinsp;=\u0026thinsp;unstable angina; n\u0026thinsp;=\u0026thinsp;number of people.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSTEMI\u0026thinsp;=\u0026thinsp;ST-segment elevation myocardial infarction; CHD\u0026thinsp;=\u0026thinsp;coronary heart disease; CABG\u0026thinsp;=\u0026thinsp;coronary artery bypass grafting; NSTE-ACS\u0026thinsp;=\u0026thinsp;non-ST-segment elevation acute coronary syndrome; PCI\u0026thinsp;=\u0026thinsp;percutaneous coronary intervention; N\u0026thinsp;=\u0026thinsp;number of people\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eHospitalization examination and concomitant medication\u003c/h2\u003e \u003cp\u003eExamination data and concomitant medications are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Compared to those of the control group, the tirofiban group had a higher red blood cell count (4.44 vs 4.33, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), hemoglobin concentration (136 vs. 133, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.029), and LVEF (61% vs. 60%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eHospitalization examination and concomitant medication\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTirofiban Group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;798)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl Group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;442)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLaboratory data, median (Q1\u0026ndash;Q3) or mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC, \u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.46 (5.38\u0026ndash;7.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.37 (5.30\u0026ndash;7.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.250\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRBC, \u0026times;10\u003csup\u003e12\u003c/sup\u003e/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.44 (4.05\u0026ndash;4.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.33 (3.98\u0026ndash;4.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHb, g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e136 (124\u0026ndash;146)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e133 (123\u0026ndash;144)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.029\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLT, \u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e210 (173\u0026ndash;252)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e214 (185\u0026ndash;253)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.141\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR, ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85.55 (70.60\u0026ndash;94.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85.10 (70.95\u0026ndash;95.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.695\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ehs-CRP, pg/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.88 (1.00-11.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.36 (0.90\u0026ndash;8.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.070\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTC, mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.42 (3.69\u0026ndash;5.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.34 (3.64\u0026ndash;4.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.314\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL, mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.73 (2.12\u0026ndash;3.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.76 (2.13\u0026ndash;3.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.890\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLp(a), mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.21(17.07\u0026ndash;77.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.61(13.50-72.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.107\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eK\u003csup\u003e+\u003c/sup\u003e, mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.04 (3.83\u0026ndash;4.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.02 (3.77\u0026ndash;4.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.419\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ehs-cTnI, pg/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (26\u0026ndash;292)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58 (24\u0026ndash;253)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.323\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLeft Ventricular Ejection Fraction, median (Q1\u0026ndash;Q3)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEF (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (55\u0026ndash;65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (51\u0026ndash;65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eConcomitant medication, (no.%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACEI/ARB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e611 (76.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e337 (76.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.898\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBeta-blocker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e566 (70.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e331 (74.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.135\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStatins\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e791 (99.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e440 (99.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.399\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eeGFR\u0026thinsp;=\u0026thinsp;estimated glomerular filtration rate; WBC\u0026thinsp;=\u0026thinsp;white blood cell; RBC\u0026thinsp;=\u0026thinsp;red blood cell; Hb\u0026thinsp;=\u0026thinsp;hemoglobin; PLT\u0026thinsp;=\u0026thinsp;platelet; TC\u0026thinsp;=\u0026thinsp;total cholesterol; LDL\u0026thinsp;=\u0026thinsp;low-density lipoprotein; Lp(a)\u0026thinsp;=\u0026thinsp;lipoprotein (a); K\u0026thinsp;+\u0026thinsp;=\u0026thinsp;potassium; hs-CRP\u0026thinsp;=\u0026thinsp;highly sensitive C reaction protein; hs-cTnI\u0026thinsp;=\u0026thinsp;highly sensitive cardiac troponin I; LVEF\u0026thinsp;=\u0026thinsp;left ventricular ejection fraction; ACEI\u0026thinsp;=\u0026thinsp;angiotensin-converting enzyme inhibitor; ARB\u0026thinsp;=\u0026thinsp;angiotensin receptor blocker.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAngiographic and procedural characteristics\u003c/h3\u003e\n\u003cp\u003eAnalysis of angiographic and procedural characteristics is presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Patients with bifurcation (15.5% vs. 10.9%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.022) and occlusion lesions (17.8% vs. 11.1%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) were more often treated with tirofiban, whereas those with long lesions were less frequently treated (92.4% vs. 95.5%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.033). Tirofiban was also more likely to be used in patients with a higher number of stent implantations (1\u0026ndash;3 vs 1\u0026ndash;2, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and in those who underwent intravascular imaging (6.4% vs. 3.2%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015). The prevalence of complex lesion components within the groups is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAngiographic and procedural characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTirofiban Group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;798)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl Group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;442)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTarget vessel, (no.%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft main artery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.063\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft anterior descending artery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e538 (67.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e287 (64.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.374\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft circumflex artery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e230 (28.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e126 (28.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.906\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRight coronary artery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e219 (27.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e112 (25.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.422\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-vessel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e612 (76.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e360 (81.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2-vessel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e179 (22.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81 (18.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.089\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3-vessel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.170\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComplex lesions, (no.%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft main artery lesion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.063\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1 bifurcation lesion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124 (15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (10.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.022\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1 ostial lesion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.687\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1 occlusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e142 (17.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1 lesion\u0026thinsp;\u0026ge;\u0026thinsp;20 mm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e737 (92.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e422 (95.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.033\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1 calcified lesion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.108\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eType of intervention, (no.%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug-eluting stent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e798 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e442 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProcedural characteristics, (no.%) / median (Q1\u0026ndash;Q3)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of stents implanted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStent length\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (22\u0026ndash;29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (23\u0026ndash;29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.473\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStent diameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.87 (2.75\u0026ndash;3.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.91 (2.67\u0026ndash;3.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.841\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIntravascular imaging, (no.%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVUS/OCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eIVUS\u0026thinsp;=\u0026thinsp;intravascular ultrasound; OCT\u0026thinsp;=\u0026thinsp;optical coherence tomography; n\u0026thinsp;=\u0026thinsp;number of people.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eComplex coronary lesions were defined as those meeting at least one of the following criteria: left main coronary artery lesion, occlusion, bifurcation lesion, ostial lesion, lesion length\u0026thinsp;\u0026gt;\u0026thinsp;20 mm, or a calcified lesion. This figure illustrates the distribution of these lesion types across study groups. Notably, lesions\u0026thinsp;\u0026gt;\u0026thinsp;20 mm in length were the most common, while left main coronary artery lesions were the least prevalent in both groups.\u003c/p\u003e\n\u003ch3\u003eHospital length of stay and medicine costs\u003c/h3\u003e\n\u003cp\u003eLOS and medicine costs are depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. There was no significant difference in LOS between the tirofiban and control groups (5.10 vs 5.11, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.555). However, the medicine costs in the tirofiban group were significantly higher than those in the control group (\u0026yen;2121 vs. \u0026yen;1579, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ens\u0026thinsp;=\u0026thinsp;no significance; ***= \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eClinical outcomes\u003c/h2\u003e \u003cp\u003eThe unadjusted and multivariate-adjusted ischemia outcomes during the 30 days after PCI are shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. In the tirofiban group, nine patients died compared to two patients in the control group (1.1% vs. 0.5%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.369; adjusted HR: 4.369, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.177). Additionally, 11 and six patients in the tirofiban and control groups, respectively, experienced either nonfatal myocardial infarction or nonfatal cerebral infarction (1.4% vs. 1.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.976; adjusted HR: 1.160, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.782). Unstable angina was recorded in 53 individuals in the tirofiban cohort compared to 30 individuals in the control cohort (6.6% vs. 6.8%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.922; adjusted HR: 1.018, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.941). Acute heart failure was observed in two individuals in the tirofiban cohort, while five individuals in the control cohort experienced this condition (0.6% vs. 1.1%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.113; adjusted HR: 0.148, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.083). In terms of composite ischemia, 73 patients in the tirofiban cohort and 38 patients in the control cohort were affected (9.1% vs. 8.6%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.745; adjusted HR: 1.219, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.342). In summary, there was no statistically significant difference in the 30-day efficacy endpoints between the different tirofiban groups.\u003c/p\u003e \u003cp\u003eBleeding outcomes are presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Major bleeding events were observed in four patients in the tirofiban group compared with two patients in the control group (0.5% vs. 0.5%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.906). Minor bleeding was reported in 26 patients in the tirofiban cohort and 13 individuals in the control cohort (3.3% vs. 2.9%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.759). Major or minor bleeding was documented in 30 patients in the tirofiban group and 15 patients in the control group (3.8% vs. 3.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.742). Overall, there were no statistically significant differences in the safety endpoints between the two groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTirofiban Group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;798)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl Group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;442)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical ischemic outcomes, (no.%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComposite ischemia (all-cause death, nonfatal myocardial infarction, nonfatal cerebral infraction, unstable angina, acute heart failure)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.745\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll-cause death\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.369\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNonfatal myocardial infarction, nonfatal cerebral infraction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.976\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnstable angina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.922\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute heart failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.113\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical bleeding outcomes, (no.%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.742\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMajor bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.906\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinor bleeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.759\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eGPI\u0026thinsp;=\u0026thinsp;glycoprotein IIb/IIIa inhibitor; n\u0026thinsp;=\u0026thinsp;number of people.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA, 30-day all-cause mortality in the tirofiban group versus control group; B, 30-day incidence of unstable angina in the tirofiban group versus control group; C, 30-day incidence of nonfatal myocardial infarction plus nonfatal cerebral infarction in the tirofiban group versus control group; D, 30-day incidence of acute heart failure in the tirofiban group versus control group. E, 30-day composite ischemic events (all-cause death, unstable angina, nonfatal cerebral infarction, acute heart failure, and nonfatal myocardial infarction) in the tirofiban group versus control group. A-E Adjusted for age, sex, LVEF, P2Y12 receptor antagonists, bifurcation lesions, occlusive lesions, lesion length\u0026thinsp;\u0026gt;\u0026thinsp;20 mm, number of stents, and intravascular ultrasound/optical coherence tomography. Multivariate Cox proportional hazard regression analysis was used to determine adjusted hazard ratios (HR) and 95% confidence intervals (CI).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup analyses\u003c/h2\u003e \u003cp\u003eSubgroup analysis revealed no significant difference in mortality between the control and tirofiban groups in the overall population (adjusted HR: 1.10, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.619). Subgroup analyses stratified by age, sex, clinical presentation, presence of diabetes mellitus, LVEF, eGFR, P2Y\u003csub\u003e12\u003c/sub\u003e receptor inhibitors, and other lesion characteristics consistently demonstrated no significant interaction effects (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA dot-whisker plot showing the association between GPI use and 30-day composite ischemic events (all-cause death, unstable angina, nonfatal cerebral infarction, acute heart failure, and nonfatal myocardial infarction).\u003c/p\u003e \u003cp\u003eHazard ratio adjusted for sex, age, P2Y12 inhibitors, and clinical presentation.\u003c/p\u003e \u003cp\u003eUA\u0026thinsp;=\u0026thinsp;unstable angina; NSTEMI\u0026thinsp;=\u0026thinsp;non-ST-segment elevation myocardial infarction; eGFR\u0026thinsp;=\u0026thinsp;estimated glomerular filtration rate; LVEF\u0026thinsp;=\u0026thinsp;left ventricular ejection fraction; IVUS\u0026thinsp;=\u0026thinsp;intravascular ultrasonography; OCT\u0026thinsp;=\u0026thinsp;optical coherence tomography; ACEI\u0026thinsp;=\u0026thinsp;angiotensin-converting enzyme inhibitor; ARB\u0026thinsp;=\u0026thinsp;angiotensin receptor blocker; CI\u0026thinsp;=\u0026thinsp;confidence interval; OR\u0026thinsp;=\u0026thinsp;odds ratio.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we evaluated whether an intensive antiplatelet regimen combining tirofiban with DAPT could reduce the occurrence of ischemic complications in NSTE-ACS patients with complex lesions undergoing PCI. The results showed that additional administration of tirofiban did not provide any significant clinical benefit for ischemic events within 30 days post-procedure.\u003c/p\u003e \u003cp\u003eThis is the first case-matched study to evaluate the effect of tirofiban in addition to DAPT on the clinical prognosis of NSTE-ACS patients with complex lesions. In previous studies, all patients who underwent PCI were enrolled regardless of the anatomical features of the target lesion. Therefore, patients with complex and non-complex lesions accounted for a certain proportion. However, our study focused exclusively on a population with complex target vessel lesions at high risk of thrombosis, making the subjects more distinctive.\u003c/p\u003e \u003cp\u003eEarlier trials assessed the effects of GPI prior to the routine use of P2Y\u003csub\u003e12\u003c/sub\u003e receptor antagonists. A meta-analysis involving six trials encompassing 29,570 participants, among which 6,637 received revascularization, demonstrated a notable decrease in the incidence of death or myocardial infarction within 30 days in NSTE-ACS patients [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, no statistical significance was observed in any of the individual studies. The trials included in this analysis were PRISM, PARAGON B, PARAGON A, PURSUIT, GUSTO IV, and PRISM-PLUS [\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In these studies, patients were treated with both aspirin and GPI, whereas all participants in our study were administered a loading dose of a P2Y\u003csub\u003e12\u003c/sub\u003e receptor blocker. A previous study confirmed that P2Y\u003csub\u003e12\u003c/sub\u003e receptors play a major role in the amplification of platelet activation and that the combination of a P2Y\u003csub\u003e12\u003c/sub\u003e receptor antagonist and aspirin has an additive effect on the inhibition of platelet activation and related platelet responses [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. As GPI are known to significantly inhibit the common final pathway of platelet aggregation by blocking the GP IIb/IIIa receptor [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], more than two-thirds of NSTE-ACS patients with complex lesions in this study were empirically treated with tirofiban by the operator to reduce the risk of thrombotic events. However, our results showed that tirofiban did not provide any additional benefits in preventing thrombotic events after PCI. We believe that one of the limitations of tirofiban is that its additional antiplatelet advantage is reduced when combined with aspirin and a P2Y\u003csub\u003e12\u003c/sub\u003e receptor antagonist. Another possible factor is its short half-life.\u003c/p\u003e \u003cp\u003eIn the era of DAPT, the effects of GPI are controversial. The On-TIME 2 trial involved STEMI patients who underwent PCI with a loading dose of 500 mg aspirin and 600 mg clopidogrel [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The clinical results of this study demonstrated better 30-day outcomes with GPI than with placebo, primarily driven by a reduction in thrombotic bailout, without an increased risk of bleeding [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In addition, the ISAR-REACT 2 trial, involving 2,022 high-risk NSTE-ACS patients, showed that GPI reduced 30-day ischemic events, exceeding expectations [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, in the subgroup analysis of NSTEMI and UA patients, improvements in mortality and ischemic outcomes were observed only in NSTEMI patients, with no difference noted in UA patients [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In the ISAR-REACT 2 trial, approximately 50% of the patients were NSTEMI, whereas only about 20% of the patients in our study were NSTEMI after propensity matching. NSTEMI patients are more prone to plaque rupture and, consequently, have a higher risk of thrombosis. This makes them more likely to benefit from GPI treatment owing to its anti-inflammatory and antithrombotic properties. However, compared with those in previous studies [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], our subgroup analyses did not yield similar results. The discrepancies may be attributed to differences in the study populations, especially the significant variation in the proportion of NSTEMI patients. To address the issue of insufficient evidence, further confirmatory trials involving NSTEMI and UA patients receiving DAPT, or even a potent DAPT strategy, may be needed to enhance the statistical power of subgroup analysis results from previous studies.\u003c/p\u003e \u003cp\u003eFew studies have been conducted to characterize complex coronary lesions, despite the increased risk of ischemic complications and the challenges of complex PCI procedures. This gap is largely owing to the lack of standardization criteria and definitions for complex coronary lesions [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The definition of complex coronary anatomical lesions in most earlier studies was based on the 1988 AHA guidelines for type B2 and C lesions. Therefore, the definition of complex lesions in our study was derived from these previous studies [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In the ISAR-REACT trial, which included stable coronary artery disease patients undergoing PCI, subgroup analysis revealed that GPI did not lead to a decrease in 30-day mortality or cardiac events among patients with complex lesions [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Another retrospective study indirectly assessed the role of GPI, finding no significant difference in the 30-day occurrence of major adverse events between NSTE-ACS patients treated with unfractionated heparin combined with GPI and those treated with bivalirudin after complex PCI [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The patients in both studies received adequate doses of aspirin and P2Y\u003csub\u003e12\u003c/sub\u003e inhibitors. In our study, patients with more complex lesions or those who had more stents implanted used GPI more frequently. However, the additional use of GPI did not reduce 30-day ischemic events. These findings provide preliminary evidence for the anti-ischemic efficacy of DAPT, even in the absence of GPIs, in patients with complex lesions.\u003c/p\u003e \u003cp\u003e These results indicate that dual antiplatelet strategies can be used in accordance with the guidelines for NSTE-ACS patients with complex lesions. However, GPI are used exclusively in cases with a significant thrombus burden; however, their use, which often depends on the intervenor\u0026rsquo;s experience, requires further standardization.\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eFirstly, this was a single-center, continuous, retrospective observational study. Owing to the nature of observational studies, the results may be affected by confounding factors. Nonetheless, we used propensity score matching for major clinical variables to adjust for confounding factors, and multivariate adjustment for outcomes was performed to support our findings. Secondly, the sample size was small. We excluded patients who had previously received antiplatelet therapy and retained only those who were first-time antiplatelet users to ensure equal onset and timing of DAPT in the study population. Finally, our results may not be generalizable to patients treated with other GP IIb/IIIa inhibitors such as abciximab and eptifibatide, because the patients in this study were treated with tirofiban alone.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn NSTE-ACS patients with complex lesions, additional tirofiban use did not improve short-term mortality and ischemic clinical outcomes but significantly increased drug costs.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eACS\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eacute coronary syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCHD\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecoronary heart disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eDAPT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003edual antiplatelet therapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eGPI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eglycoprotein IIb/IIIa inhibitor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNSTE-ACS\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enon-ST-segment elevation acute coronary syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNSTEMI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enon-ST-segment elevation myocardial infarction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePCI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epercutaneous coronary intervention\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eSTEMI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eST-segment elevation myocardial infarction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eUA\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eunstable angina\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted without external financial support. All aspects of the research, including design, data handling, analysis, and manuscript preparation, were independently managed by the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors and Affiliations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China\u003c/p\u003e\n\u003cp\u003eHubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China\u003c/p\u003e\n\u003cp\u003eRu Sun, Ling Zhou, Jia Cheng, Chen Chen, Jiangtao Yan, Chunxia Zhao\u0026nbsp;\u0026amp; Feng Wang\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. RS, FW, and CZ conceived the research topic and framework. RS, LZ, and JC conducted data cleaning and analysis for the cohort study. CC and JY completed the statistical analysis. RS, LZ, and JC drafted the manuscript. FW, CC, and CZ reviewed the data and revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence to Feng Wang.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research adhered to the ethical standards established by the 1964 Declaration of Helsinki and its subsequent revisions. The institutional review board of Tongji Hospital provided ethical approval for this work (TJ-IRB202407077). All patients signed the informed consent to participate in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors affirm that patients provided informed consent regarding publishing their data and images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations of competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the Health Information Management Department of Tongji Hospital, but restrictions apply to the availability of these data, which were used under institutional data governance protocols for the current study, and thus are not publicly accessible. Data may however be obtained from the corresponding author upon reasonable scientific request and with formal approval from the Ethics Committee of Tongji Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eReed G, Rossi J, Cannon C. Acute myocardial infarction. Lancet. 2007;389(10065):197\u0026ndash;210.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBhatt D, Lopes R, Harrington R. Diagnosis and treatment of acute coronary syndromes: A review. JAMA. 2022;327(7):662\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLawton J, Tamis-Holland J, Bangalore S, Bates E, Beckie T, Bischoff J, et al. ACC/AHA/SCAI guideline for coronary artery revascularization: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. 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Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med. 1998;339:436\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoliterno D, PARAGON B International Steering Committee. Patient-specific dosing of IIb/IIIa antagonists during acute coronary syndromes: Rationale and design of the PARAGON B study. Am Heart J. 2000;139(4):563\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePARAGON Investigators. International, randomized, controlled trial of lamifiban (a platelet glycoprotein IIb/IIIa inhibitor), heparin, or both in unstable angina. Circulation. 1998;97(24):2386\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePARAGON Investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. N Engl J Med. 1998;338:1488\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePRISM Study Investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med. 1998;338:1498\u0026ndash;505.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCapodanno D, Angiolillo D. Personalized antiplatelet therapies for coronary artery disease: what the future holds. Eur Heart J. 2023;44(32):3059\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharifi-Rad J, Sharopov F, Ezzat S, Zam W, Ademiluyi A, Oyeniran O, et al. An updated review on glycoprotein IIb/IIIa inhibitors as antiplatelet agents: Basic and clinical perspectives. High Blood Press Cardiovasc Prev. 2023;30:93\u0026ndash;107.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan\u0026rsquo;t Hof A, Berg J, Heestermans T, Dill T, Funck R, van Werkum W, et al. Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): A multicentre, double-blind, randomized controlled trial. Lancet. 2008;372:537\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollet J, Thiele H, Barbato E, Barth\u0026eacute;l\u0026eacute;my O, Bauersachs J, Bhatt D, et al. 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021;42:1289\u0026ndash;367.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKirtane A, Doshi D, Leon M, Lasala J, Ohman E, O\u0026rsquo;Neill W, et al. Treatment of higher-risk patients with an indication for revascularization: Evolution within the field of contemporary percutaneous coronary intervention. Circulation. 2016;134:422\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRyan T, Faxon D, Gunnar R, Kennedy J, King S 3rd, Loop F, et al. Guidelines for percutaneous transluminal coronary angioplasty: A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Percutaneous Transluminal Coronary Angioplasty). Circulation. 1988;78:486\u0026ndash;502.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKastrati A, Mehilli J, Sch\u0026uuml;hlen H, Dirschinger J, Dotzer F, ten Berg J, et al. A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med. 2004;350:232\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCortese B, Micheli A, Picchi A, Bandinelli L, Brizi M, Severi S, et al. Safety and efficacy of a prolonged bivalirudin infusion after urgent and complex percutaneous coronary interventions: A descriptive study. Coron Artery Dis. 2009;20:348\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"NSTE-ACS, complex lesion, glycoprotein IIb/IIIa inhibitors, antiplatelet therapy, antithrombotic therapy","lastPublishedDoi":"10.21203/rs.3.rs-6313276/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6313276/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePreventing ischemic events is a critical concern for patients undergoing percutaneous coronary intervention (PCI). Glycoprotein IIb/IIIa inhibitors can significantly reduce short-term ischemic risk in ST-segment elevation myocardial infarction patients after PCI. However, their effectiveness in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients with complex lesions remains unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study included 1240 NSTE-ACS patients with complex coronary lesions. Patients receiving dual antiplatelet therapy (DAPT) after PCI, with or without tirofiban, were compared. The efficacy endpoint was a composite of 30-day ischemic events, while the safety endpoint was any occurrence of bleeding.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe addition of tirofiban did not improve the 30-day ischemic outcomes among NSTE-ACS patients with complex lesions, and no significant enhancement was observed in these outcomes following multivariate adjustment (9.1% vs. 8.6%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.745; adjusted HR: 1.219, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.342). The subgroup analyses showed consistent results. Although additional tirofiban treatment did not increase bleeding risk (3.8% vs. 3.4%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.742), the medicine costs in the tirofiban group were significantly higher than those in the control group (\u0026yen;2121 vs. \u0026yen;1579, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eNSTE-ACS patients with complex lesions undergoing PCI may not benefit from additional tirofiban. However, the use of tirofiban significantly increased the medicine costs. The use of DAPT provides adequate antithrombotic protection in NSTE-ACS patients with complex lesions after PCI.\u003c/p\u003e","manuscriptTitle":"Adjunctive tirofiban fails to reduce 30-day ischemic events in NSTE-ACS patients with complex coronary lesions after PCI: a retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 01:28:25","doi":"10.21203/rs.3.rs-6313276/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-05-18T00:05:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-12T00:02:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"236524290331179454249365492315158759534","date":"2025-05-07T21:17:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"26886394536505957521673310636158500658","date":"2025-05-05T23:42:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-05T17:34:39+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-09T10:16:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-08T20:35:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-05T04:43:27+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2025-04-05T04:42:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1cd639b2-d688-4acd-96ab-b8a3c64d456b","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-05-13T01:28:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-13 01:28:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6313276","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6313276","identity":"rs-6313276","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}