Efficacy and Safety of Tirofiban in Patients with Acute branch atheromatous disease after intravenous thrombolysis

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Efficacy and Safety of Tirofiban in Patients with Acute branch atheromatous disease after intravenous thrombolysis | 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 Efficacy and Safety of Tirofiban in Patients with Acute branch atheromatous disease after intravenous thrombolysis Lanying He, Yinglin Liu, Junying Li, Lili Zhang, Fangfang Zhou, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6373730/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background and purpose Acute branch atheromatous disease (BAD) frequently leads to early neurological deterioration (END), a factor that often predicts an unfavorable outcome. Our study aimed to assess evaluate efficacy and safety of intravenous tirofiban for improving the functional outcome in patients with acute BAD after intravenous thrombolysis. Methods In this retrospective study, acute BAD patients who received intravenous thrombolysis followed by tirofiban between January 2019 and December 2023 were enrolled. The demographics, clinical data, and functional outcomes were compared among different groups. A modified ranking scale (mRS) ≤ 2 was defined as favorable outcome at 90 days. The safety outcome was the incidence of any intracranial hemorrhage and tirofiban-associated complications. Results A total of 111 patients were included, 32(28.83%) patients experienced END, 34(30.63%) patients received tirofiban after thrombolysis, tirofiban was independently associated with favorable prognosis (aOR, 6.55; 95%CI, 1.10-39.15; P = 0.039) for acute BAD patients with intravenous thrombolysis at 90 days, there was no statistical difference in safety between the tirofiban and no tirofiban groups (P > 0.05). Conclusions Tirofiban had shown promising potential as an adjunctive therapy in acute BAD patients who received intravenous thrombolysis. Tirofiban was associated with improved clinical outcomes without increasing any bleeding risks and tirofiban-associated complications acute ischemic stroke branch atheromatous disease tirofiban outcome early neurological deterioration INTRODUCTION Branch atheromatous disease (BAD), a concept initially outlined by Caplan in 1989, is now recognized as a distinct clinical entity thanks to the advancements in neuroimaging technology[ 1 – 3 ].Characterized by a single subcortical infarct in the territories of perforator arteries without significant stenosis of the major parent artery, acute BAD constitutes 20.4% of all acute ischemic stroke (AIS) among Asian populations [ 2 – 4 ]. Acute BAD was caused by the occlusion of the perforating artery's orifice by a parent arterial plaque or by proximal atherosclerotic occlusion of the perforating artery itself[ 1 – 6 ]. Acute BAD was associated with a notably high incidence of early neurological deterioration (END), which was a significant predictor of an unfavorable outcome [ 7 , 8 ]. The prevalence of END in acute BAD was reported to 26.8–37.5%. A previous study had shown that traditional antiplatelet drugs plus argatroban could decrease the risk of END, and improve clinical prognosis in acute BAD with non-thrombolytic [ 9 ]. According to the guidelines for the treatment of AIS, patients with acute BAD are not prescribed traditional antiplatelet drugs within 24 hours after intravenous thrombolytic, and few patients add argatroban within 24 hours after intravenous thrombolytic[ 10 , 11 ], on the other hand, many studies had shown that intravenous thrombolytic could not prevent the occurrence of END [ 7 , 8 , 12 ], and there were few researches on salvage treatment after the occurrence of END. Tirofiban, a selective and reversible inhibitor of the glycoprotein IIb/IIIa receptors on platelets, is potentially more effective than traditional agents like aspirin or clopidogrel by inhibiting the final common pathway of platelet aggregation at a pathophysiological level. Clinical studies had indicated that tirofiban could increase the rate of recanalization and improve functional outcomes in AIS undergoing endovascular therapy without increasing the risk of bleeding [ 13 – 16 ]. Additionally, many randomized clinical trial involving AIS without large or medium-sized vessel occlusion had also reported the efficacy of tirofiban [ 17 – 19 ]. In really clinical practice, tirofiban could be prescribed after END in acute BAD, but it was still unclear whether tirofiban could improve the clinical prognosis. Therefore, the aim of this retrospective study was to evaluate efficacy and safety of tirofiban for improving the functional outcome in patients with acute BAD after intravenous thrombolytic. METHODS Study Population This was a single-center retrospective study, we included consecutive AIS patients admitted to The Second People’s Hospital of Chengdu who were treated with intravenous thrombolytic between January 2019 and December 2023. AIS were identified using the International Classification of Diseases, Tenth Revision code (ICD-10). The ICD-10 diagnosis code I.63 had been confirmed as highly reliable [ 20 ]. All AIS patients were manually screened. Four clinicians collected information by examining the Electronic Medical Record (EMR) system. A data extraction form was created and utilized to document patient characteristics. Ethical approval for this study was obtained from the ethics committees of the Second People’s Hospital of Chengdu (NO.CDSPH-AF-SQ.04-01.1). The data of AIS patient with intravenous thrombolytic were carefully reviewed by neurologists, the location of the infarction was obtained based on cranial magnetic resonance imaging (MRI). BAD involving the lenticulostriate arteries (LSA) was identified as infarctions exceeding 15 mm in diameter on axial view, spanning across at least three slices; whereas BAD affecting the paramedian pontine arteries (PPA) was characterized by singular unilateral infarctions reaching the ventral pons surface, and no ipsilateral responsible proximal vessel stenosis . Inclusion criteria Patients were included in the study only if they fulfilled all the following criteria: 1. Admission for first-ever AIS; 2.Receiving intravenous thrombolytic; 3. Infarcts more than 15 mm in diameter on axial slice and visible for three or more axial slices in the LSA or isolated unilateral infarcts extending to the ventral surface of the pons on DWI; 4.Exhibiting a single acute ischemic lesion in the cerebral hemisphere that corresponded to their clinical presentation; 5. Receiving conventional treatment, including antiplatelet drugs, lipid-lowering drugs, and blood pressure management aspirin and lipid-lowering drugs in accordance with the guidelines for the treatment of AIS. Exclusion criteria The exclusion criteria:1. Cardioembolic stroke; 2.Cardiac diseases (include acute myocardial infarction, a history of tachyarrhythmia/bradyarrhythmia or atrial fibrillation);3.Severe pulmonary disease, renal failure(estimated glomerular filtration rate<30ml/min.1.73m 2 ) and active malignancies; 4.Cerebral hemorrhage, fever(≥ 38℃), hypoxia༈arterial oxyhemoglobin saturation < 90%);5. MRI contraindications. Data collection The comprehensive data were collected, encompassing demographic details such as age and sex, smoking habits, and medical histories including hypertension, dyslipidemia, and diabetes mellitus, glucose (GLU), triglycerides (TG), total cholesterol (Tcho), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C). National Institutes of Health Stroke Scale (NIHSS) scores on admission, the onset to treatment time (OTT) and END were extracted from the patients' medical records. The use of tirofiban was recorded, according to the medical record, the clinician decided whether to add tirofiban based on the patient's wishes, financial status, and bleeding risk. END was identified as a increase in the NIHSS score ≥ 2 within 72 hours after stroke, excluding cases of hemorrhagic conversion or additional infarcts in separate vascular regions. 90-day modified Rankin Scale (mRS) were assessed through follow-up records or the patients' outpatient medical records. Outcomes The differences in safety and efficacy were compared between tirofiban and the no-tirofiban groups. Efficacy was defined as mRS ≤ 2 at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours, assessed using the Heidelberg Bleeding Classification [ 21 ]. Additional safety variables included the incidence of any radiologically detected intracranial hemorrhage, mortality within 90 days, the occurrence of serious adverse events associated with tirofiban. Statistical Analysis Patients were divided into two groups: the tirofiban group and the no-tirofiban group, as well as the favorable prognosis group and unfavorable prognosis group. In the univariate analysis, demographic characteristics of the two subgroups were compared. The Pearson chi-squared test and Fisher's exact two-sided test were used for categorical variables, the Student's t-test was used for continuous variables. The Kolmogorov-Smirnov test was applied to determine the distribution of continuous variables, the Mann-Whitney U test was utilized for non-normally distributed variables. Multivariate analysis was conducted to assess the relationship between factors and favorable prognosis. The outcomes were presented as adjusted odds ratios (aOR) along with the respective 95% confidence intervals (CI). Data analysis was performed using SPSS software (version 27.0), and P<0.05 was considered statistically significant. RESULTS Baseline characteristics of the study subjects The EMRs of 764 AIS patients who underwent thrombolysis were retrospectively reviewed. The electronic medical records (EMRs) were meticulously reviewed to identify patients who had been diagnosed with acute BAD. After reviewing the patient’s history, clinical characteristics, risk factors and cranial MRI, we found that 34 patients had contraindications for MRI examination, 127 patients met the diagnostic criteria for BAD, while 6 patients experienced bleeding after thrombolysis, among them, 2 patients had asymptomatic intracranial bleeding (petechial hemorrhage), 3 had mild gastrointestinal bleeding, 1 had extensive subcutaneous bleeding, 10 patients had incomplete medical records. After the manual review, 111 patients with acute BAD were identified (111/764, 14.53%), which comprised of 79(58.30%) male, the mean age of these patients was 70.14 ± 13.47 years old (range: 25–90 years old). Among them, 62 patients had hypertension, 21 had diabetes, 31 had hyperlipidemia, 45 current smoking, 36 current alcohol drinking. The median NIHSS scores was 4, the mean OTT was 166.08 minutes. 32(28.83%,32/111) patients experienced END, 34(30.63%, 34/111) patients received tirofiban after thrombolysis, with 22 of 34 in the END group and 12 of 34 in the no-END group. Baseline characteristics of patients in the no tirofiban and tirofiban groups were compared (Table 1 ). At baseline, compared to the no tirofiban group, patients in the tirofiban group were younger(65.94 ± 14.21 vs 72.00 ± 12.79, P = 0.013), and the proportion of END was higher ( 64.71% vs 12.99%, P < 0.001). Patients with END were more likely to be prescribed tirofiban, 22 (68.75%, 22/32) patients received tirofiban after experiencing END, and 12 (15.19%, 12/79) received tirofiban as a preventive measure. Vascular comorbidities of sex, diabetes, hypertension, hyperlipidemia, current smoking, current alcohol drinking were not different between no tirofiban and tirofiban groups, and there were no significant difference in NIHSS score on admission, OTT, GLU, TG, Tcho, HDL-C, LDL-C, pre-stroke tatin use, pre-stroke antiplatelet (P > 0.05). Table 1 Comparison of baseline characteristics between patients with no tirofiban and tirofiban groups. no tirofiban group (77) tirofiban (34) OR(95%CI) P* Age, y (Mean SD) 72.00 ± 12.79 65.94 ± 14.21 0.013 NIHSS score, (Mean SD) 5.47 ± 4.89 5.21 ± 4.89 0.218 OTT, (Mean SD) 156.44 ± 97.42 187.91 ± 159.09 0.550 Males, n(%) 55(64.94) 24(70.59) 0.96(0.40–2.33) 0.550 Hypertension, n(%) 44(57.14) 18(52.94) 0.84(0.38–1.90) 0.681 Diabetes, n (%) 13(16.88) 8(23.53) 1.51(0.56–4.08) 0.283 Hyperlipidemia, n(%) 21(27.27) 10(29.41) 1.11(0.46–2.71) 0.494 Current Smoking, n(%) 30(38.96) 15(44.12) 0.23(0.55–02.80) 0.380 Current alcohol drinking, n(%) 25(32.47) 11(32.35) 1.00(0.42–2.36) 0.586 GLU, mmol/l (Mean SD) 5.87 ± 2.10 6.14 ± 2.41 0.376 TG, mmol/l (Mean SD) 1.41 ± 0.70 1.38 ± 0.68 0.367 Tcho, mmol/l (Mean SD) 4.42 ± 0.98 4.80 ± 1.53 0.175 HDL-C, mmol/l (Mean SD) 1.14 ± 0.39 1.20 ± 0.31 0.081 LDL-C, mmol/l (Mean SD) 2.54 ± 0.82 2.85 ± 1.37 0.322 Pre-stroke medications use Antiplatelet, n (%) 2(2.56) 1(2.91) 1.14(10.10-12.97) 0.670 Tatin, n (%) 13(6.88) 3(8.82) 0.48(0.13–1.80) 0.209 END, n (%) 10(12.99) 22(64.71) 12.28(4.67–32.32) < 0.001 3 months mRS ≤ 2, n (%) 56(72.73) 23(67.65) 0.78(0.33–1.88) 0.371 Bold indicates p-values less than 0.05. *Comparison between no tirofiban and tirofiban groups. For continuous variables, the data are presented as mean ± standard deviation (SD). For categorical variables, the data are expressed as frequency (percentage). To calculate P values, we employed the Pearson chi-squared test, Fisher's exact two-sided test, and Student's t-test as appropriate. Mann-Whitney U test was utilized for non-normally distributed variables. Impact of variables on functional outcome 79(79/111, 71.17%) patients had favorable prognosis at 3 months (Table 2 ), at baseline, patients with favorable prognosis showed significantly lower prevalence of END (16.48% vs 59.38; P < 0.001), there were no significant difference in age, NIHSS score on admission, OTT, sex, diabetes, hypertension, hyperlipidemia, current smoking, current alcohol drinking, GLU, TG, Tcho, HDL-C, LDL-C, pre-stroke tatin use, pre-stroke antiplatelet between unfavorable prognosis and favorable prognosis groups (P > 0.05). Table 2 Comparison of baseline characteristics between patients with unfavorable prognosis and favorable prognosis groups. unfavorable prognosis(32) favorable prognosis (79) OR(95%CI) P* Age, y (Mean SD) 68.42 ± 13.35 70.91 ± 13.70 0.194 NIHSS score, (Mean SD) 6.48 ± 5.69 5.01 ± 4.12 0.397 OTT, (Mean SD) 201.26 ± 171.73 152.58 ± 91.38 0.373 Males, n(%) 24(75.00) 55(69.62) 0.76(0.30–1.94) 0.571 Hypertension, n(%) 18(56.25) 44(55.70) 0.98(0.43–2.24) 0.958 Diabetes, n (%) 5(15.63) 16(20.25) 1.37(0.46–4.12) 0.573 Hyperlipidemia, n(%) 8(25.00) 23(29.11) 1.23(0.48–3.14) 0.662 Current Smoking, n(%) 16(50.00) 29(36.71) 0.58(0.25–01.33) 0.196 Current alcohol drinking, n(%) 12(337.50) 24(30.38) 10.73(0.31–1.72) 0.468 GLU, mmol/l (Mean SD) 5.77 ± 1.55 5.96 ± 2.34 0.755 TG, mmol/l (Mean SD) 1.31 ± 0.59 1.44 ± 0.73 0.526 Tcho, mmol/l (Mean SD) 4.53 ± 1.21 4.54 ± 1.17 0.907 HDL-C, mmol/l (Mean SD) 1.28 ± 0.53 1.11 ± 0.25 0.131 LDL-C, mmol/l (Mean SD) 2.9 ± 1.05 2.65 ± 1.01 0.833 Pre-stroke medications use Antiplatelet, n (%) 1(3.13) 2(2.53) 0.81(0.70–9.21) 0.861 Tatin, n (%) 6(18.75) 10(12.66) 0.63(0.21–1.90) 0.408 END, n (%) 19(59.38) 13(16.45) 0.135(0.54 − 0.34) < 0.001 Tirofiban, n (%) 11(34.38) 23(29.11) 0.78(0.33–1.88) 0.586 Bold indicates p-values less than 0.05. *Comparison between unfavorable prognosis and favorable prognosis groups. For continuous variables, the data are presented as mean ± standard deviation (SD). For categorical variables, the data are expressed as frequency (percentage). Pearson chi-squared test, Fisher's exact two-sided test, and Student's t-test as appropriate. Mann-Whitney U test was utilized for non-normally distributed variables. The proportion of patients with END was signiffcantly higher in patients with unfavorable prognosis (59.38% vs 16.45%). The rate of favorable prognosis was 40.63% (13/32) for patients with END, which was significantly lower than patients without END (83.54%;66/79; P < 0.01). Patients who experienced END were more likely to be treated with tirofiban, with a total of 22 patients in the END group receiving tirofiban, of whom 11 had a favorable prognosis(50.00%), which was significantly higher than the patients who did not receive tirofiban (20%;2/10;P < 0.01). Variables associated with clinical prognosis were included in the multivariate analysis, after adjustment for age, NIHSS score on admission, OTT, sex, diabetes, hypertension, hyperlipidemia, current smoking, current alcohol drinking, GLU, TG, Tcho, HDL-C, LDL-C, pre-stroke medications use, the results showed that END had a negative effect on favorable prognosis (aOR, 0.03; 95%CI, 0.01–0.19; P < 0.001), tirofiban was independently associated with favorable prognosis (aOR, 6.55; 95%CI, 1.10-39.15; P = 0.039) for acute BAD with intravenous thrombolytic at 90 days (Table 3 ). Table 3 Multivariable models showing the association between factors and favorable prognosis OR (95% CI) P* Tirofiban 6.55 (1.10–39.15) 0.039 END 0.03(0.01–0.19) < 0.001 Bold indicates p-values less than 0.05. *Multivariable adjusted for age, NIHSS score on admission, OTT, sex,diabetes, hypertension, hyperlipidemia, current smoking, current alcohol drinking, GLU, TG, Tcho, HDL-C, LDL-C, pre-stroke medications use. Safety outcomes There was no statistical difference in safety between the tirofiban and no tirofiban groups(P > 0.05), both groups had no sICH, 1 aICH in the tirofiban group and 3 aICH in the non-tirofiban group, 2 mild thrombocytopenia in the tirofiban group, no thrombocytopenia in the non-tirofiban group, 1 subcutaneous bleeding in the tirofiban group, 3 in non-tirofiban group. DISCUSSION In this study, we found that tirofiban was associated with favorable prognosis in acute BAD patients undergoing intravenous thrombolysis at 90 days. Tirofiban did not increase the risk of any ICH and tirofiban-associated complications. The study showed that 28.83% patients experienced END, 34(30.63%) patients received tirofiban after thrombolysis, with 22 in the END group and 12 in the non-END group, patients who experienced END were more likely to be treated with tirofiban. BAD is a form of atherosclerotic pathology that impacts vessels branching vertically from larger arteries. As described by Caplan, the atherothrombotic mechanism in BAD is anticipated to result in cerebral infarctions across multiple branch regions originating from the lesion site[ 1 ], thrombosis primarily caused by two mechanisms: plaque rupture and endothelial erosion[ 22 ]. The issue of reocclusion following successful reperfusion is a significant challenge in the management of cerebral infarction and warrants thorough discussion. The early use of antiplatelet drugs within 24 hours after intravenous thrombolysis has always been a perplexing clinical issue. The guidelines for AIS that anticoagulants and antiplatelet drugs should be avoided within 24 hours after thrombolytic therapy[ 23 – 25 ]. The 2018 guidelines from the American Heart Association and the American Stroke Association for the early management of AIS suggested that the use of antiplatelet drugs could be considered within the first 24 hours following intravenous thrombolysis, depending on individual risk assessment and the balance of potential benefits and risks [ 26 ]. Consequently, it is crucial to identify patients with a low bleeding risk who might benefit from early antiplatelet therapy to guide decisions on its administration. A previous study had indicated that the use of low-dose tirofiban within the first 24 hours after intravenous thrombolysis in patients experiencing END did not increase the risk of symptomatic intracranial hemorrhage (ICH), ICH, and mortality. Moreover, it appeared to be associated with neurological improvement at 3 months [ 20 ]. Unlike these trials[ 20 , 27 ], which enrolled all AIS patients with intravenous thrombolysis, our study targeted acute BAD after intravenous thrombolysis, acute BAD was strongly associated with END and unfavourable outcomes. This may explain the efficacy outcome of our trial. Our study showed that tirofiban did not increase the risk of intracranial hemorrhage or peripheral hemorrhage or tirofiban-associated complications, these findings were in line with those of other glycoprotein IIb/IIIa antagonist studies. In some small observational studies, the results found that the combination of thrombolysis and tirofiban treatment for AIS could significantly reduce the occurrence of END, furthermore, tirofiban as a salvage therapy for END can markedly improve clinical outcomes without increasing the risk of symptomatic ICH [ 28 , 29 ]. The CLEAR-ER trial demonstrated that the combination of intravenous thrombolysis with eptifibatide was safe, and there was a favorable outcomes in the eptifibatide group[ 30 , 31 ]. Tirofiban and eptifibatide are competitive and selective inhibitors of the glycoprotein IIb/IIIa receptor, and platelet function can return to normal within 7 hours after their discontinuation. These properties might make the glycoprotein IIb/IIIa inhibitors as a viable alternative to aspirin in certain patients within the first 24 hours post-intravenous thrombolysis. CONCLUSIONS Our study was distinctive in focusing on acute BAD patients undergoing intravenous thrombolysis, this types of stroke was relatively prevalent, and associated with unfavorable outcomes. Treatment of acute BAD is crucial. Regrettably, there are no existing management guidelines for END, and in really clinical practice, there are no specific interventions to reverse this clinical deficits and prevent adverse outcomes. Our findings strongly suggested that early tiroffban treatment in acute BAD patients with intravenous thrombolysis might be both safe and effective, but it cannot be recommended for general use before prospective randomized clinical trials are completed. This study may provide a new perspective for future research on END after intravenous thrombolysis in acute BAD. Limitation Some limitations of this study merit consideration. Firstly, this was a retrospective study, which might lead to bias. Secondly, the number of patients analyzed in this study was relatively small, and the optimal strategy for administering tirofiban after intravenous thrombolysis in acute BAD still requires further investigation through large-sample and multicenter studies. Thirdly, due to the limited number of cases, the study did not analyze the impact of prophylactic use of tirofiban on clinical outcomes before END and also did not analyze difference of traditional antiplatelet drug (dual antiplatelet drugs or single antiplatelet drugs) combined tirofiban in acute BAD, in this study, the majority of patients used tirofiban as a salvage therapy for END. Despite these limitations, the results of this study have certain guiding value for the management after intravenous thrombolysis in BAD-related stroke. Abbreviations CI: Confidence Interval; M: Mean; OR: Odds Ratio; SD: Standard Deviation; BAD: Branch atheromatous disease; END:Early neurological deterioration; AIS:acute ischemic stroke; ICD-10:Tenth Revision code; MRI:Cranial magnetic resonance imaging;LSA:Lenticulostriate arteries;PPA:Paramedian pontine arteries;GLU:Glucose; TG:Triglycerides; Tcho:Total cholesterol; HDL-C:High-density lipoprotein cholesterol; LDL-C:Low-density lipoprotein cholesterol; NIHSS: Health Stroke Scale; OTT:onset to treatment time; mRS:Modified Rankin Scale; EMRs: Electronic medical records Declarations Ethics approval and consent to participate Ethical approval for this study was granted by the Medical and Health Research Ethics Committee at the Second People's Hospital of Chengdu, and the study was conducted in compliance with the Declaration of Helsinki. Written informed consent was secured from all participants or their legally authorized representatives. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This work was funded by the Sichuan Medical and Health Care Promotion Institute (KY2022QN0355), which is not involved in the database management (collection, analysis, interpretation of data) and has no access to patient information. The funding body did not participate in designing the study or writing the manuscript. The study protocol has undergone peer-review process by the funding body. Authors ’ contributions LYH was in charge of the study's concept, data collection, analysis, and drafting the initial manuscript. YLL,JYL,FFZ and YZ contributed to data analysis and interpretation. LLZ and LW focused on data analysis. JW and LL supervised the study's concept and design, data analysis, and interpretation. 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Safety and efficacy of Tirofiban combined with Endovascular treatment in acute ischaemic stroke. Eur J Neurol. 2019;26(8):1105–10. 10.1111/ene.13946 . Yang J, Wu Y, Gao X, Bivard A, Levi CR, Parsons MW, Lin L, INSPIRE Study Group. Intraarterial versus intravenous Tirofiban as an adjunct to Endovascular Thrombectomy for acute ischemic stroke. Stroke. 2020;51(10):2925–33. 10.1161/STROKEAHA.120.029994 . Kokotailo RA, Hill MD. Coding of stroke and stroke risk factors using International Classification of Diseases, revisions 9 and 10. Kokotailo RA, Hill MD. Stroke. 2005;36(8):1776–81. 10.1161/01.STR.0000174293.17959.a1 . von Kummer R, Broderick JP, Campbell BC, et al. The Heidelberg Bleeding Classification: classification of bleeding events after ischemic stroke and reperfusion therapy. Stroke. 2015;46(10):2981–6. 10.1161/STROKEAHA.115.010049 . Hansson GK, Engl. J Med. 2005;352(16):1685–95. 10.1056/NEJMra043430 . Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D. ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317–29. 10.1056/NEJMoa0804656 . von Kummer R, Broderick JP, Campbell BC, Demchuk A, Goyal M, Hill MD, Treurniet KM, Majoie CB, Marquering HA, Mazya MV, San Román L, Saver JL, Strbian D, Whiteley W, Hacke W. The heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy. Stroke. 2015;46(10):2981–6. 10.1161/STROKEAHA.115.010049 . Kwiatkowski TG, Libman RB, Frankel M, Tilley BC, Morgenstern LB, Lu M, Broderick JP, Lewandowski CA, Marler JR, Levine SR, Brott T. Effects of tissue plasminogen activator for acute ischemic stroke at one year. National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study Group.N Engl. J Med. 1999;340(23):1781–7. 10.1056/NEJM199906103402302 . Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL, American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46–110. 10.1161/STR.0000000000000158 . Wu C, Sun C, Wang L, Lian Y, Xie N, Huang S, Zhao W, Ren M, Wu D, Ding J, Song H, Wang Y, Ma Q, Ji X. Low-Dose Tirofiban Treatment Improves Neurological Deterioration Outcome After Intravenous Thrombolysis. Stroke. 2019;50(12):3481–7. 10.1161/STROKEAHA.119.026240 . Liu Y, Li S, Hao D, Zhang Z, Yi Y, Fang J, Lin W, Zhang M. Clinical safety and possible efficacy of tirofiban in combination with intravenous thrombolysis by recombinant tissue plasminogen activator for early treatment of capsular warning syndrome (CWS). Front Neurosci. 2022;16:1026127. 10.3389/fnins.2022.1026127 . Straub S, Junghans U, Jovanovic V, Wittsack HJ, Seitz RJ, Siebler M. Systemic thrombolysis with recombinant tissue plasminogen activator and tirofiban in acute middle cerebral artery occlusion. Stroke. 2004;35(3):705–9. 10.1161/01.STR.0000117094.41638.EE . Pancioli AM, Adeoye O, Schmit PA, Khoury J, Levine SR, Tomsick TA, Sucharew H, Brooks CE, Crocco TJ, Gutmann L, Hemmen TM, Kasner SE, Kleindorfer D, Knight WA, Martini S, McKinney JS, Meurer WJ, Meyer BC, Schneider A, Scott PA, Starkman S, Warach S, Broderick JP. CLEAR-ER Investigators. Combined approach to lysis utilizing eptiffbatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial. Stroke. 2013;44(9):2381–7. 10.1161/STROKEAHA.113.001059 . Epub 2013 Jul 25. Adeoye O, Sucharew H, Khoury J, Tomsick T, Khatri P, Palesch Y, Schmit PA, Pancioli AM, Broderick JP, CLEAR-ER, IMS III. Part 2 Investigators. Recombinant tissue-type plasminogen activator plus eptifibatide versus recombinant tissue-type plasminogen activator alone in acute ischemic stroke: propensity score-matched post hoc analysis. Stroke. 2015;46(2):461–4. 10.1161/STROKEAHA.114.006743 . 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-6373730","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":453130054,"identity":"1b570ac9-fd1f-471b-a7e3-a25ab665f288","order_by":0,"name":"Lanying He","email":"","orcid":"","institution":"The Second People’s Hospital of Chengdu","correspondingAuthor":false,"prefix":"","firstName":"Lanying","middleName":"","lastName":"He","suffix":""},{"id":453130055,"identity":"31584744-8df5-4967-bcb1-18896093985a","order_by":1,"name":"Yinglin Liu","email":"","orcid":"","institution":"The Second People’s Hospital of Chengdu","correspondingAuthor":false,"prefix":"","firstName":"Yinglin","middleName":"","lastName":"Liu","suffix":""},{"id":453130056,"identity":"f0a7665d-29e0-45cf-b4e6-5700db61caf1","order_by":2,"name":"Junying Li","email":"","orcid":"","institution":"The Second People’s Hospital of Chengdu","correspondingAuthor":false,"prefix":"","firstName":"Junying","middleName":"","lastName":"Li","suffix":""},{"id":453130057,"identity":"c23b4685-de23-4d8c-a78d-89e44d6d6f4e","order_by":3,"name":"Lili Zhang","email":"","orcid":"","institution":"The Second People’s Hospital of Chengdu","correspondingAuthor":false,"prefix":"","firstName":"Lili","middleName":"","lastName":"Zhang","suffix":""},{"id":453130059,"identity":"f51c4a10-d8e3-41f8-8327-844ebfa85430","order_by":4,"name":"Fangfang Zhou","email":"","orcid":"","institution":"The Second People’s Hospital of Chengdu","correspondingAuthor":false,"prefix":"","firstName":"Fangfang","middleName":"","lastName":"Zhou","suffix":""},{"id":453130062,"identity":"498907b5-cca1-4b52-b407-de00a6c596c9","order_by":5,"name":"Lu Wang","email":"","orcid":"","institution":"The Second People’s Hospital of Chengdu","correspondingAuthor":false,"prefix":"","firstName":"Lu","middleName":"","lastName":"Wang","suffix":""},{"id":453130066,"identity":"85768da3-cf67-4203-8a91-f15cb46153cd","order_by":6,"name":"Yao Zhong","email":"","orcid":"","institution":"The Second People’s Hospital of Chengdu","correspondingAuthor":false,"prefix":"","firstName":"Yao","middleName":"","lastName":"Zhong","suffix":""},{"id":453130070,"identity":"eb828514-ff82-4e5c-a9ad-314879f6fdd7","order_by":7,"name":"Jian Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABD0lEQVRIie2RMUvDUBDHX3kQl6dZLwjFj3AlEDoE/SAu9yhkiqXgIliwUEgWoWs/hlBwNXDQLpGuGZ+bQ4cUFwuivs6S2FHw/aYb/r877k4Ih+OvAiiEL2WBdBMrW7A5SAnyjEamTLpB7iV40CQsS9y+ZBziWp1Ba3L1zK/90flQVNR7IE/qBSuBYhxfNjcfJn3AwXVnTgMk5elHPi6MWCZXkwYlKtIIAaWeAi2RQFnlhLAz4WZlvdkrdzoDnb8Tgl5MFUKrUqWhAWR9r1ggEYYof1Euqk1kj7zS86PMKgV1ge2RqWWXYJaGb/Bxq5/Yr3u7zy/lz5hNPY4bFYt3+vMN1BzfI7d1e8DhcDj+O98edl+6y4wOzAAAAABJRU5ErkJggg==","orcid":"","institution":"The Second People’s Hospital of Chengdu","correspondingAuthor":true,"prefix":"","firstName":"Jian","middleName":"","lastName":"Wang","suffix":""},{"id":453130073,"identity":"2f5839f3-180e-4f97-8962-9dd8e58d2ca0","order_by":8,"name":"Lun Luo","email":"","orcid":"","institution":"The Second People’s Hospital of Chengdu","correspondingAuthor":false,"prefix":"","firstName":"Lun","middleName":"","lastName":"Luo","suffix":""}],"badges":[],"createdAt":"2025-04-04 06:38:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6373730/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6373730/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82296261,"identity":"b774c5de-8e2e-4148-a668-967dabda4ea2","added_by":"auto","created_at":"2025-05-08 19:38:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":747960,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6373730/v1/9ec9cc18-56df-4431-b045-27907c6ae2b0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy and Safety of Tirofiban in Patients with Acute branch atheromatous disease after intravenous thrombolysis","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eBranch atheromatous disease (BAD), a concept initially outlined by Caplan in 1989, is now recognized as a distinct clinical entity thanks to the advancements in neuroimaging technology[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].Characterized by a single subcortical infarct in the territories of perforator arteries without significant stenosis of the major parent artery, acute BAD constitutes 20.4% of all acute ischemic stroke (AIS) among Asian populations [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Acute BAD was caused by the occlusion of the perforating artery's orifice by a parent arterial plaque or by proximal atherosclerotic occlusion of the perforating artery itself[\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAcute BAD was associated with a notably high incidence of early neurological deterioration (END), which was a significant predictor of an unfavorable outcome [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The prevalence of END in acute BAD was reported to 26.8\u0026ndash;37.5%. A previous study had shown that traditional antiplatelet drugs plus argatroban could decrease the risk of END, and improve clinical prognosis in acute BAD with non-thrombolytic [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. According to the guidelines for the treatment of AIS, patients with acute BAD are not prescribed traditional antiplatelet drugs within 24 hours after intravenous thrombolytic, and few patients add argatroban within 24 hours after intravenous thrombolytic[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], on the other hand, many studies had shown that intravenous thrombolytic could not prevent the occurrence of END [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and there were few researches on salvage treatment after the occurrence of END.\u003c/p\u003e \u003cp\u003eTirofiban, a selective and reversible inhibitor of the glycoprotein IIb/IIIa receptors on platelets, is potentially more effective than traditional agents like aspirin or clopidogrel by inhibiting the final common pathway of platelet aggregation at a pathophysiological level. Clinical studies had indicated that tirofiban could increase the rate of recanalization and improve functional outcomes in AIS undergoing endovascular therapy without increasing the risk of bleeding [\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Additionally, many randomized clinical trial involving AIS without large or medium-sized vessel occlusion had also reported the efficacy of tirofiban [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn really clinical practice, tirofiban could be prescribed after END in acute BAD, but it was still unclear whether tirofiban could improve the clinical prognosis. Therefore, the aim of this retrospective study was to evaluate efficacy and safety of tirofiban for improving the functional outcome in patients with acute BAD after intravenous thrombolytic.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eThis was a single-center retrospective study, we included consecutive AIS patients admitted to The Second People\u0026rsquo;s Hospital of Chengdu who were treated with intravenous thrombolytic between January 2019 and December 2023. AIS were identified using the International Classification of Diseases, Tenth Revision code (ICD-10). The ICD-10 diagnosis code I.63 had been confirmed as highly reliable [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. All AIS patients were manually screened. Four clinicians collected information by examining the Electronic Medical Record (EMR) system. A data extraction form was created and utilized to document patient characteristics. Ethical approval for this study was obtained from the ethics committees of the Second People\u0026rsquo;s Hospital of Chengdu (NO.CDSPH-AF-SQ.04-01.1).\u003c/p\u003e \u003cp\u003eThe data of AIS patient with intravenous thrombolytic were carefully reviewed by neurologists, the location of the infarction was obtained based on cranial magnetic resonance imaging (MRI). BAD involving the lenticulostriate arteries (LSA) was identified as infarctions exceeding 15 mm in diameter on axial view, spanning across at least three slices; whereas BAD affecting the paramedian pontine arteries (PPA) was characterized by singular unilateral infarctions reaching the ventral pons surface, and no ipsilateral responsible proximal vessel stenosis .\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion criteria\u003c/h3\u003e\n\u003cp\u003ePatients were included in the study only if they fulfilled all the following criteria: 1. Admission for first-ever AIS; 2.Receiving intravenous thrombolytic; 3. Infarcts more than 15 mm in diameter on axial slice and visible for three or more axial slices in the LSA or isolated unilateral infarcts extending to the ventral surface of the pons on DWI; 4.Exhibiting a single acute ischemic lesion in the cerebral hemisphere that corresponded to their clinical presentation; 5. Receiving conventional treatment, including antiplatelet drugs, lipid-lowering drugs, and blood pressure management aspirin and lipid-lowering drugs in accordance with the guidelines for the treatment of AIS.\u003c/p\u003e\n\u003ch3\u003eExclusion criteria\u003c/h3\u003e\n\u003cp\u003eThe exclusion criteria:1. Cardioembolic stroke; 2.Cardiac diseases (include acute myocardial infarction, a history of tachyarrhythmia/bradyarrhythmia or atrial fibrillation);3.Severe pulmonary disease, renal failure(estimated glomerular filtration rate\u0026lt;30ml/min.1.73m\u003csup\u003e2\u003c/sup\u003e) and active malignancies; 4.Cerebral hemorrhage, fever(\u0026ge;\u0026thinsp;38℃), hypoxia༈arterial oxyhemoglobin saturation\u0026thinsp;\u0026lt;\u0026thinsp;90%);5. MRI contraindications.\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eThe comprehensive data were collected, encompassing demographic details such as age and sex, smoking habits, and medical histories including hypertension, dyslipidemia, and diabetes mellitus, glucose (GLU), triglycerides (TG), total cholesterol (Tcho), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C). National Institutes of Health Stroke Scale (NIHSS) scores on admission, the onset to treatment time (OTT) and END were extracted from the patients' medical records. The use of tirofiban was recorded, according to the medical record, the clinician decided whether to add tirofiban based on the patient's wishes, financial status, and bleeding risk.\u003c/p\u003e \u003cp\u003eEND was identified as a increase in the NIHSS score\u0026thinsp;\u0026ge;\u0026thinsp;2 within 72 hours after stroke, excluding cases of hemorrhagic conversion or additional infarcts in separate vascular regions. 90-day modified Rankin Scale (mRS) were assessed through follow-up records or the patients' outpatient medical records.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe differences in safety and efficacy were compared between tirofiban and the no-tirofiban groups. Efficacy was defined as mRS\u0026thinsp;\u0026le;\u0026thinsp;2 at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours, assessed using the Heidelberg Bleeding Classification [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Additional safety variables included the incidence of any radiologically detected intracranial hemorrhage, mortality within 90 days, the occurrence of serious adverse events associated with tirofiban.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003ePatients were divided into two groups: the tirofiban group and the no-tirofiban group, as well as the favorable prognosis group and unfavorable prognosis group. In the univariate analysis, demographic characteristics of the two subgroups were compared. The Pearson chi-squared test and Fisher's exact two-sided test were used for categorical variables, the Student's t-test was used for continuous variables. The Kolmogorov-Smirnov test was applied to determine the distribution of continuous variables, the Mann-Whitney U test was utilized for non-normally distributed variables. Multivariate analysis was conducted to assess the relationship between factors and favorable prognosis. The outcomes were presented as adjusted odds ratios (aOR) along with the respective 95% confidence intervals (CI). Data analysis was performed using SPSS software (version 27.0), and P\u0026lt;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eBaseline characteristics of the study subjects\u003c/h2\u003e \u003cp\u003eThe EMRs of 764 AIS patients who underwent thrombolysis were retrospectively reviewed. The electronic medical records (EMRs) were meticulously reviewed to identify patients who had been diagnosed with acute BAD. After reviewing the patient\u0026rsquo;s history, clinical characteristics, risk factors and cranial MRI, we found that 34 patients had contraindications for MRI examination, 127 patients met the diagnostic criteria for BAD, while 6 patients experienced bleeding after thrombolysis, among them, 2 patients had asymptomatic intracranial bleeding (petechial hemorrhage), 3 had mild gastrointestinal bleeding, 1 had extensive subcutaneous bleeding, 10 patients had incomplete medical records.\u003c/p\u003e \u003cp\u003eAfter the manual review, 111 patients with acute BAD were identified (111/764, 14.53%), which comprised of 79(58.30%) male, the mean age of these patients was 70.14\u0026thinsp;\u0026plusmn;\u0026thinsp;13.47 years old (range: 25\u0026ndash;90 years old). Among them, 62 patients had hypertension, 21 had diabetes, 31 had hyperlipidemia, 45 current smoking, 36 current alcohol drinking. The median NIHSS scores was 4, the mean OTT was 166.08 minutes.\u003c/p\u003e \u003cp\u003e32(28.83%,32/111) patients experienced END, 34(30.63%, 34/111) patients received tirofiban after thrombolysis, with 22 of 34 in the END group and 12 of 34 in the no-END group. Baseline characteristics of patients in the no tirofiban and tirofiban groups were compared (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). At baseline, compared to the no tirofiban group, patients in the tirofiban group were younger(65.94\u0026thinsp;\u0026plusmn;\u0026thinsp;14.21 vs 72.00\u0026thinsp;\u0026plusmn;\u0026thinsp;12.79, P\u0026thinsp;=\u0026thinsp;0.013), and the proportion of END was higher ( 64.71% vs 12.99%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Patients with END were more likely to be prescribed tirofiban, 22 (68.75%, 22/32) patients received tirofiban after experiencing END, and 12 (15.19%, 12/79) received tirofiban as a preventive measure. Vascular comorbidities of sex, diabetes, hypertension, hyperlipidemia, current smoking, current alcohol drinking were not different between no tirofiban and tirofiban groups, and there were no significant difference in NIHSS score on admission, OTT, GLU, TG, Tcho, HDL-C, LDL-C, pre-stroke tatin use, pre-stroke antiplatelet (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\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\u003eComparison of baseline characteristics between patients with no tirofiban and tirofiban groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\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\u003eno tirofiban group (77)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003etirofiban (34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR(95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, y (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72.00\u0026thinsp;\u0026plusmn;\u0026thinsp;12.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.94\u0026thinsp;\u0026plusmn;\u0026thinsp;14.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.013\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNIHSS score, (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.47\u0026thinsp;\u0026plusmn;\u0026thinsp;4.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.21\u0026thinsp;\u0026plusmn;\u0026thinsp;4.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.218\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOTT, (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e156.44\u0026thinsp;\u0026plusmn;\u0026thinsp;97.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e187.91\u0026thinsp;\u0026plusmn;\u0026thinsp;159.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.550\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMales, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55(64.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24(70.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.96(0.40\u0026ndash;2.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.550\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44(57.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(52.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.84(0.38\u0026ndash;1.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.681\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(16.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(23.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.51(0.56\u0026ndash;4.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.283\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperlipidemia, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21(27.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(29.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.11(0.46\u0026ndash;2.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.494\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent Smoking, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30(38.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(44.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.23(0.55\u0026ndash;02.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.380\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent alcohol drinking, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25(32.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(32.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.00(0.42\u0026ndash;2.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.586\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGLU, mmol/l (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.87\u0026thinsp;\u0026plusmn;\u0026thinsp;2.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.14\u0026thinsp;\u0026plusmn;\u0026thinsp;2.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.376\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTG, mmol/l (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.367\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTcho, mmol/l (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.175\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDL-C, mmol/l (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.081\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL-C, mmol/l (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.85\u0026thinsp;\u0026plusmn;\u0026thinsp;1.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.322\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-stroke medications use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntiplatelet, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(2.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(2.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.14(10.10-12.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.670\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTatin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(6.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(8.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.48(0.13\u0026ndash;1.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.209\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEND, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(12.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22(64.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.28(4.67\u0026ndash;32.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 months mRS\u0026thinsp;\u0026le;\u0026thinsp;2, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56(72.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(67.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.78(0.33\u0026ndash;1.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.371\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\u003eBold indicates p-values less than 0.05.\u003c/p\u003e \u003cp\u003e*Comparison between no tirofiban and tirofiban groups. For continuous variables, the data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). For categorical variables, the data are expressed as frequency (percentage). To calculate P values, we employed the Pearson chi-squared test, Fisher's exact two-sided test, and Student's t-test as appropriate. Mann-Whitney U test was utilized for non-normally distributed variables.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eImpact of variables on functional outcome\u003c/h2\u003e \u003cp\u003e79(79/111, 71.17%) patients had favorable prognosis at 3 months (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), at baseline, patients with favorable prognosis showed significantly lower prevalence of END (16.48% vs 59.38; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), there were no significant difference in age, NIHSS score on admission, OTT, sex, diabetes, hypertension, hyperlipidemia, current smoking, current alcohol drinking, GLU, TG, Tcho, HDL-C, LDL-C, pre-stroke tatin use, pre-stroke antiplatelet between unfavorable prognosis and favorable prognosis groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\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\u003eComparison of baseline characteristics between patients with unfavorable prognosis and favorable prognosis groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\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\u003eunfavorable prognosis(32)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003efavorable prognosis (79)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR(95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, y (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68.42\u0026thinsp;\u0026plusmn;\u0026thinsp;13.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.91\u0026thinsp;\u0026plusmn;\u0026thinsp;13.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.194\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNIHSS score, (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.48\u0026thinsp;\u0026plusmn;\u0026thinsp;5.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.01\u0026thinsp;\u0026plusmn;\u0026thinsp;4.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.397\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOTT, (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e201.26\u0026thinsp;\u0026plusmn;\u0026thinsp;171.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e152.58\u0026thinsp;\u0026plusmn;\u0026thinsp;91.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.373\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMales, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24(75.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55(69.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.76(0.30\u0026ndash;1.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.571\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18(56.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44(55.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.98(0.43\u0026ndash;2.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.958\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(15.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(20.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.37(0.46\u0026ndash;4.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.573\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperlipidemia, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(25.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(29.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.23(0.48\u0026ndash;3.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.662\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent Smoking, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(50.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29(36.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.58(0.25\u0026ndash;01.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.196\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent alcohol drinking, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(337.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24(30.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10.73(0.31\u0026ndash;1.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.468\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGLU, mmol/l (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.77\u0026thinsp;\u0026plusmn;\u0026thinsp;1.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.96\u0026thinsp;\u0026plusmn;\u0026thinsp;2.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.755\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTG, mmol/l (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.526\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTcho, mmol/l (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.53\u0026thinsp;\u0026plusmn;\u0026thinsp;1.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.54\u0026thinsp;\u0026plusmn;\u0026thinsp;1.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.907\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHDL-C, mmol/l (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.131\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDL-C, mmol/l (Mean SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.65\u0026thinsp;\u0026plusmn;\u0026thinsp;1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.833\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-stroke medications use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntiplatelet, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(3.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(2.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.81(0.70\u0026ndash;9.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.861\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTatin, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(18.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(12.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.63(0.21\u0026ndash;1.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.408\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEND, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(59.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(16.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.135(0.54\u0026thinsp;\u0026minus;\u0026thinsp;0.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTirofiban, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(34.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(29.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.78(0.33\u0026ndash;1.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.586\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\u003eBold indicates p-values less than 0.05.\u003c/p\u003e \u003cp\u003e*Comparison between unfavorable prognosis and favorable prognosis groups. For continuous variables, the data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). For categorical variables, the data are expressed as frequency (percentage). Pearson chi-squared test, Fisher's exact two-sided test, and Student's t-test as appropriate. Mann-Whitney U test was utilized for non-normally distributed variables.\u003c/p\u003e \u003cp\u003eThe proportion of patients with END was signiffcantly higher in patients with unfavorable prognosis (59.38% vs 16.45%). The rate of favorable prognosis was 40.63% (13/32) for patients with END, which was significantly lower than patients without END (83.54%;66/79; P\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e \u003cp\u003ePatients who experienced END were more likely to be treated with tirofiban, with a total of 22 patients in the END group receiving tirofiban, of whom 11 had a favorable prognosis(50.00%), which was significantly higher than the patients who did not receive tirofiban (20%;2/10;P\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e \u003cp\u003eVariables associated with clinical prognosis were included in the multivariate analysis, after adjustment for age, NIHSS score on admission, OTT, sex, diabetes, hypertension, hyperlipidemia, current smoking, current alcohol drinking, GLU, TG, Tcho, HDL-C, LDL-C, pre-stroke medications use, the results showed that END had a negative effect on favorable prognosis (aOR, 0.03; 95%CI, 0.01\u0026ndash;0.19; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), tirofiban was independently associated with favorable prognosis (aOR, 6.55; 95%CI, 1.10-39.15; P\u0026thinsp;=\u0026thinsp;0.039) for acute BAD with intravenous thrombolytic at 90 days (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\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\u003eMultivariable models showing the association between factors and favorable prognosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\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\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTirofiban\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.55 (1.10\u0026ndash;39.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.039\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEND\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.03(0.01\u0026ndash;0.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\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\u003eBold indicates p-values less than 0.05.\u003c/p\u003e \u003cp\u003e*Multivariable adjusted for age, NIHSS score on admission, OTT, sex,diabetes, hypertension, hyperlipidemia, current smoking, current alcohol drinking, GLU, TG, Tcho, HDL-C, LDL-C, pre-stroke medications use.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSafety outcomes\u003c/h2\u003e \u003cp\u003eThere was no statistical difference in safety between the tirofiban and no tirofiban groups(P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), both groups had no sICH, 1 aICH in the tirofiban group and 3 aICH in the non-tirofiban group, 2 mild thrombocytopenia in the tirofiban group, no thrombocytopenia in the non-tirofiban group, 1 subcutaneous bleeding in the tirofiban group, 3 in non-tirofiban group.\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this study, we found that tirofiban was associated with favorable prognosis in acute BAD patients undergoing intravenous thrombolysis at 90 days. Tirofiban did not increase the risk of any ICH and tirofiban-associated complications.\u003c/p\u003e \u003cp\u003eThe study showed that 28.83% patients experienced END, 34(30.63%) patients received tirofiban after thrombolysis, with 22 in the END group and 12 in the non-END group, patients who experienced END were more likely to be treated with tirofiban. BAD is a form of atherosclerotic pathology that impacts vessels branching vertically from larger arteries. As described by Caplan, the atherothrombotic mechanism in BAD is anticipated to result in cerebral infarctions across multiple branch regions originating from the lesion site[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], thrombosis primarily caused by two mechanisms: plaque rupture and endothelial erosion[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The issue of reocclusion following successful reperfusion is a significant challenge in the management of cerebral infarction and warrants thorough discussion. The early use of antiplatelet drugs within 24 hours after intravenous thrombolysis has always been a perplexing clinical issue. The guidelines for AIS that anticoagulants and antiplatelet drugs should be avoided within 24 hours after thrombolytic therapy[\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The 2018 guidelines from the American Heart Association and the American Stroke Association for the early management of AIS suggested that the use of antiplatelet drugs could be considered within the first 24 hours following intravenous thrombolysis, depending on individual risk assessment and the balance of potential benefits and risks [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Consequently, it is crucial to identify patients with a low bleeding risk who might benefit from early antiplatelet therapy to guide decisions on its administration. A previous study had indicated that the use of low-dose tirofiban within the first 24 hours after intravenous thrombolysis in patients experiencing END did not increase the risk of symptomatic intracranial hemorrhage (ICH), ICH, and mortality. Moreover, it appeared to be associated with neurological improvement at 3 months [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Unlike these trials[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], which enrolled all AIS patients with intravenous thrombolysis, our study targeted acute BAD after intravenous thrombolysis, acute BAD was strongly associated with END and unfavourable outcomes. This may explain the efficacy outcome of our trial.\u003c/p\u003e \u003cp\u003eOur study showed that tirofiban did not increase the risk of intracranial hemorrhage or peripheral hemorrhage or tirofiban-associated complications, these findings were in line with those of other glycoprotein IIb/IIIa antagonist studies. In some small observational studies, the results found that the combination of thrombolysis and tirofiban treatment for AIS could significantly reduce the occurrence of END, furthermore, tirofiban as a salvage therapy for END can markedly improve clinical outcomes without increasing the risk of symptomatic ICH [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The CLEAR-ER trial demonstrated that the combination of intravenous thrombolysis with eptifibatide was safe, and there was a favorable outcomes in the eptifibatide group[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Tirofiban and eptifibatide are competitive and selective inhibitors of the glycoprotein IIb/IIIa receptor, and platelet function can return to normal within 7 hours after their discontinuation. These properties might make the glycoprotein IIb/IIIa inhibitors as a viable alternative to aspirin in certain patients within the first 24 hours post-intravenous thrombolysis.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eOur study was distinctive in focusing on acute BAD patients undergoing intravenous thrombolysis, this types of stroke was relatively prevalent, and associated with unfavorable outcomes. Treatment of acute BAD is crucial. Regrettably, there are no existing management guidelines for END, and in really clinical practice, there are no specific interventions to reverse this clinical deficits and prevent adverse outcomes. Our findings strongly suggested that early tiroffban treatment in acute BAD patients with intravenous thrombolysis might be both safe and effective, but it cannot be recommended for general use before prospective randomized clinical trials are completed. This study may provide a new perspective for future research on END after intravenous thrombolysis in acute BAD.\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eLimitation\u003c/h2\u003e \u003cp\u003eSome limitations of this study merit consideration. Firstly, this was a retrospective study, which might lead to bias. Secondly, the number of patients analyzed in this study was relatively small, and the optimal strategy for administering tirofiban after intravenous thrombolysis in acute BAD still requires further investigation through large-sample and multicenter studies. Thirdly, due to the limited number of cases, the study did not analyze the impact of prophylactic use of tirofiban on clinical outcomes before END and also did not analyze difference of traditional antiplatelet drug (dual antiplatelet drugs or single antiplatelet drugs) combined tirofiban in acute BAD, in this study, the majority of patients used tirofiban as a salvage therapy for END. Despite these limitations, the results of this study have certain guiding value for the management after intravenous thrombolysis in BAD-related stroke.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCI: Confidence Interval; M: Mean; OR: Odds Ratio; SD: Standard Deviation; BAD: Branch atheromatous disease; END:Early neurological deterioration; AIS:acute ischemic stroke; ICD-10:Tenth Revision code; MRI:Cranial magnetic resonance imaging;LSA:Lenticulostriate arteries;PPA:Paramedian pontine arteries;GLU:Glucose; TG:Triglycerides; Tcho:Total cholesterol; HDL-C:High-density lipoprotein cholesterol; LDL-C:Low-density lipoprotein cholesterol; NIHSS: Health Stroke Scale; OTT:onset to treatment time; mRS:Modified Rankin Scale; EMRs: Electronic medical records\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval for this study was granted by the Medical and Health Research Ethics Committee at the Second People's Hospital of Chengdu, and the study was conducted in compliance with the Declaration of Helsinki. Written informed consent was secured from all participants or their legally authorized representatives.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was funded by the Sichuan Medical and Health Care Promotion Institute (KY2022QN0355), which is not involved in the database management (collection, analysis, interpretation of data) and has no access to patient information. The funding body did not participate in designing the study or writing the manuscript. The study protocol has undergone peer-review process by the funding body.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e’\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLYH was in charge of the study's concept, data collection, analysis, and drafting the initial manuscript. YLL,JYL,FFZ and YZ contributed to data analysis and interpretation. LLZ and LW focused on data analysis. JW and LL supervised the study's concept and design, data analysis, and interpretation. All authors reviewed and approved the final manuscript for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all patients and their families for generously consenting to use of human tissues in this research.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCaplan LR. Intracranial branch atheromatous disease: a neglected, Understudied, and UNDERUSED concept. Neurology. 1989;39(9):1246\u0026ndash;50. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/wnl.39.9.1246\u003c/span\u003e\u003cspan address=\"10.1212/wnl.39.9.1246\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKwan MW-M, Mak W, Cheung RT-F, Ho SL. Ischemic stroke related to intracranial branch atheromatous disease and comparison with large and small artery diseases. 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Stroke. 2015;46(2):461\u0026ndash;4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/STROKEAHA.114.006743\u003c/span\u003e\u003cspan address=\"10.1161/STROKEAHA.114.006743\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\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-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"acute ischemic stroke, branch atheromatous disease, tirofiban, outcome, early neurological deterioration","lastPublishedDoi":"10.21203/rs.3.rs-6373730/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6373730/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground and purpose\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAcute branch atheromatous disease (BAD) frequently leads to early neurological deterioration (END), a factor that often predicts an unfavorable outcome. Our study aimed to assess evaluate efficacy and safety of intravenous tirofiban for improving the functional outcome in patients with acute BAD after intravenous thrombolysis.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003e In this retrospective study, acute BAD patients who received intravenous thrombolysis followed by tirofiban between January 2019 and December 2023 were enrolled. The demographics, clinical data, and functional outcomes were compared among different groups. A modified ranking scale (mRS)\u0026thinsp;\u0026le;\u0026thinsp;2 was defined as favorable outcome at 90 days. The safety outcome was the incidence of any intracranial hemorrhage and tirofiban-associated complications.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA total of 111 patients were included, 32(28.83%) patients experienced END, 34(30.63%) patients received tirofiban after thrombolysis, tirofiban was independently associated with favorable prognosis (aOR, 6.55; 95%CI, 1.10-39.15; P\u0026thinsp;=\u0026thinsp;0.039) for acute BAD patients with intravenous thrombolysis at 90 days, there was no statistical difference in safety between the tirofiban and no tirofiban groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTirofiban had shown promising potential as an adjunctive therapy in acute BAD patients who received intravenous thrombolysis. Tirofiban was associated with improved clinical outcomes without increasing any bleeding risks and tirofiban-associated complications\u003c/p\u003e","manuscriptTitle":"Efficacy and Safety of Tirofiban in Patients with Acute branch atheromatous disease after intravenous thrombolysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-08 19:22:25","doi":"10.21203/rs.3.rs-6373730/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-05-21T11:13:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"299913302682631194437063099287017506134","date":"2025-05-20T07:36:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"244492913382554506422747795285621757918","date":"2025-05-10T09:32:13+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-05T08:27:51+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-29T14:55:22+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-09T20:56:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-09T10:53:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-04-09T10:52:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c75dfbc3-c778-4a37-8739-63ed9162d6a8","owner":[],"postedDate":"May 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-05-08T19:22:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-08 19:22:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6373730","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6373730","identity":"rs-6373730","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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