Clopidogrel-Based vs. Aspirin-Based Double Antithrombotic Therapy Following Percutaneous Coronary Intervention with Stent in Patients on Oral Anticoagulation. A Post-Hoc Analysis of the Perseo Registry

Clopidogrel-Based vs. Aspirin-Based Double Antithrombotic Therapy Following Percutaneous Coronary Intervention with Stent in Patients on Oral Anticoagulation. 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A Post-Hoc Analysis of the Perseo Registry andrea rubboli, graziella pompei, salvatore de rosa, paolo calabrò, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8574706/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Apr, 2026 Read the published version in Journal of Thrombosis and Thrombolysis → Version 1 posted You are reading this latest preprint version Abstract In patients on oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI), clopidogrel is currently the preferred antiplatelet agent to be given in double antithrombotic therapy (DAT). To explore whether aspirin could be an alternative option, a post-hoc analysis of the Italian, multi-center, prospective PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) registry was performed. Out of the 989 patients included in the analysis, 769 (78%) received clopidogrel and 220 (22%) aspirin. Baseline characteristics were largely comparable between the two groups, particularly as regards the indications for PCI and OAC, with acute coronary syndrome and atrial fibrillation respectively, being the most common, the number of stents implanted, and the use of direct oral anticoagulants and proton-pump inhibitors. At a median follow-up of 12.3 months, the primary outcome of net adverse cardiac events (NACE), including major adverse cardiac/cerebral events (MACCE) and major bleeding was similar with clopidogrel-based and aspirin-based DAT (19.1% vs. 20.0%; p = 0.770). Secondary outcomes of MACCE, all-cause death, cardiac death, non-fatal myocardial infarction, stent thrombosis, non-fatal stroke/transient ischemic attack, target vessel revascularization, and major and clinically relevant bleeding were also comparable. Multivariable analyses confirmed no association between type of DAT and outcomes. Survival analyses showed overlapping event rates between clopidogrel-based and aspirin-baed DAT. In patients on OAC undergoing PCI, no significant difference in the occurrence of NACE was observed between clopidogrel-based and aspirin-based DAT. While waiting for further data, individualized physician’s choice of the DAT regimen appears indicated. Oral anticoagulation percutaneous coronary intervention coronary artery disease clopidogrel aspirin Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Based on the design of the five randomized clinical trials WOEST (1), PIONEER AF-PCI (2), RE-DUAL PCI (3), AUGUSTUS (4), and ENTRUST-AF PCI (5), which investigated the optimal antithrombotic therapy in patients on oral anticoagulation (OAC), mostly for atrial fibrillation (AF), undergoing percutaneous coronary intervention with stent (PCI), clopidogrel should be the preferred antiplatelet agent to be given in conjunction with OAC in double antithrombotic therapy (DAT) following an initial course of triple antithrombotic therapy (TAT) of OAC, clopidogrel, and aspirin (6–8). Owing to the potential for clopidogrel non-responsiveness (9), as well as for its pharmacological interactions with drugs commonly used in patients with coronary heart disease, such as atorvastatin (10), which may both hamper its antiplatelet effect, exploring whether an aspirin-based DAT may instead be an option appears valuable (11). Two recent analyses carried out in East Asian patients, whose susceptibility to both thrombosis and bleeding is known to be different from that of Caucasian (12), reported no significant differences either on efficacy or safety when aspirin is given instead of clopidogrel in DAT following PCI in patients on OAC (13, 14). Nonetheless, additional evidence would be of importance to further clarify this issue. With this aim, we performed a post-hoc analysis of the Italian, multi-center, prospective PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) registry (15), where patients on OAC undergoing PCI were enrolled, to compare the clinical outcomes of a clopidogrel-based vs. an aspirin-based DAT regimen. METHODS Study design and clinical endpoints. The multi-center, prospective, observational PERSEO registry (ClinicalTrials.gov Identifier: NCT03392948) was conducted at twenty-five centers in Italy, and enrolled consecutive patients on OAC for various indications, including AF, venous thromboembolism, left ventricular thrombus, and mechanical heart valves, undergoing PCI (15). Age < 18 years and lack of informed signed consent were the only exclusion criteria (15). In accordance with the observational design of the study, the pharmacological and interventional management before, during, and after PCI was entirely at the operator’s discretion (15). All clinical variables were recorded in an electronic Case Report Form (eCRF) following anonymization of patient details by assigning a unique study identifier (15). An independent dedicated society (Advice Pharma Group Srl, Milan, Italy) provided the eCRF and stored the data (15). The PERSEO registry was endorsed by the Italian Society of Interventional Cardiology (SICI-GISE) and was approved by the Ethic Committees of each participating center. For the purpose of this post-hoc analysis, patients who received clopidogrel and aspirin in the context of DAT following the initial course of TAT, were identified and compared as regards the occurrence of net adverse clinical events (NACE), including major adverse cardiac/cerebral events (MACCE) and major bleeding (primary outcome). MACCE included urgent and unplanned target vessel revascularization (TVR), non-fatal myocardial infarction (MI), stent thrombosis, non-fatal stroke/transient ischemic attack (TIA), and all-cause death. Secondary outcomes, including MACCE, all-cause death, cardiac death, non-fatal MI, non-fatal stroke/TIA, TVR, and major and clinically relevant bleeding were also compared. Stent thrombosis was defined according to the Academic Research Consortium (ARC) definition as definite, probable, and possible (16). Bleeding events were classified according to the Bleeding Academic Research Consortium (BARC) criteria as major (BARC 3 and 5), and clinically relevant (BARC 2–5) (17). By performing a landmark analysis with the date of TAT discontinuation identified as baseline, the median follow-up time was calculated based on the duration of DAT. Patients whose DAT regimen was modified during follow-up were included, however only the first DAT regimen was considered. Follow-up for these patients was censored at the time the initial DAT regimen was discontinued to switch to an alternative regimen. Patients who died in hospital while receiving TAT were excluded from the analysis as they did not receive any DAT. Statistical analysis. Categorical baseline data are presented as numbers and percentage (n, %) and analyzed with Chi-squared Monte-Carlo test. Continuous data were first tested for normality using the Shapiro-Wilk test, for which P > 0.05 was considered as normally distributed and P < 0.05 as non-normal. Normally distributed data are presented as mean and standard deviation (SD), and were validated with Levene’s test for equality of variance before analyzing with the independent T-test. Non-normally distributed data are presented as median and interquartile range (IQR), and were analyzed by the Mann-Whitney U Monte-Carlo test. To analyze the impact of independent variables on follow-up outcomes, Kaplan-Meier analysis was conducted along with Log-rank test to determine difference between groups. Kaplan Meier survival analysis was performed for the primary composite outcome of NACE, for which time-to-first event was designated as the disease-free survival time in years. Cox regression was further performed separately for each component of the primary composite outcome, yielding hazard ratios (HR) with 95% confidence intervals (CI). Multivariable models were constructed to adjust for potential pre-specified confounding factors resulting significant at univariable analysis. All statistical analyses were performed on the Statistical Package for the Social Sciences (SPSS V.29, IBM Corporation). Significance was predetermined at the level two-tailed p < 0.05. RESULTS Of the 1,234 patients enrolled in the PERSEO registry (18), six who experienced in-hospital death during TAT and 239 who never received DAT, were excluded from the analysis. Therefore, the final study population consisted of 989 patients who initiated DAT after an initial period of TAT, of whom 769 (78%) received clopidogrel and 220 (22%) received aspirin (Fig. 1). Baseline characteristics (Table 1). No differences were observed between the two groups receiving clopidogrel-based and aspirin-based DAT, with the exception of median age which was significantly higher in the clopidogrel group. The indications for both PCI and OAC were comparable, with acute coronary syndrome (ACS) and AF respectively, being the most common. The proportions of use of both direct oral anticoagulants (DOAC) and proton-pump inhibitors (PPI) were also comparable in the two groups. The CHA₂DS₂-VASc score, which was calculated as well as the HAS-BLED score only in patients with AF, was significantly higher in the clopidogrel group. The radial approach was used significantly less in the clopidogrel group. No differences were observed in the number of stents implanted, with most patients receiving one or two stents. Primary and secondary outcomes (Table 2) . At a median follow-up of 12.3 months, the primary outcome of NACE was similar in the clopidogrel-based and aspirin-based DAT groups. Secondary outcomes of MACCE, all-cause death, cardiac death, non-fatal MI, stent thrombosis, non-fatal stroke/TIA, TVR, and major and clinically relevant bleeding were also comparable. Bleeding events, including major bleeding and clinically relevant bleeding, were similar in both groups. Overall, no significant differences were observed between clopidogrel-based and aspirin-based DAT regimens across primary and secondary outcomes. Univariable, multivariable, and survival analysis. At the univariable Cox regression analysis, clopidogrel-based vs. aspirin-based DAT was not associated with a significant difference in the risk of NACE, and this remained non-significant after adjustment for age, chronic kidney disease (CKD), anaemia, number of implanted stents, and type of OAC, i.e., vitamin K antagonist (VKA) vs. direct oral anticoagulants (DOAC) (Table 3). Age emerged as a significant predictor of increased risk of NACE, and this association persisted in multivariable analysis (Table 3, Fig. 2). CKD and anaemia were also strong predictors of increased risk of NACE in both univariable and multivariable models (Table 3, Fig. 2), as well as was the number of stents implanted (Table 3, Fig. 2). The use of DOAC rather than VKA was associated with a reduced risk of NACE at both univariable and multivariable analysis (Table 3, Fig. 2). Both CHA 2 DS 2 -VASc and HAS-BLED scores showed a significant association with an increased risk of NACE at univariable analysis, but did not retain significance after adjustment (Table 3, Fig. 2). Clopidogrel-based vs. aspirin-based DAT was not associated with a significant difference in the risk of MACE, all-cause mortality, cardiac death, and stroke/TIA at both unadjusted and adjusted analysis (Table 4). Bleeding outcomes also did not differ between the two treatment strategies (Table 4). Overall, after adjustment for key clinical covariates, no clinical outcome showed a significant difference in risk between clopidogrel-based and aspirin-based DAT (Table 4). At survival analysis, both clopidogrel-based and aspirin-based DAT groups showed a similar risk profile for the cumulative incidence of NACE over the entire duration of DAT (p log-rank= 0.756), with a steady accumulation of events during the initial months of follow-up (Fig. 3A). At the 1-year landmark analysis, the cumulative incidence trajectories of the clopidogrel-based and aspirin-based DAT regimens remained substantially overlapping, with no significant differences between the two groups (p log-rank p=0.552) (Fig. 3B). DISCUSSION The main findings of this post-hoc analysis of the Italian, multi-center, prospective PERSEO registry, in which a clopidogrel-based vs. an aspirin-based DAT regimen following an initial course of TAT in OAC patients undergoing PCI were compared, are as follows: 1) no significant differences were observed in NACE, nor in either efficacy (MACCE, all-cause death, cardiac death, non-fatal myocardial infarction, stent thrombosis, non-fatal stroke/TIA, and TVR) or safety (major and clinically relevant bleeding) outcomes, 2) NACE-free survival rates were comparable between the two DAT regimens, 3) regardless of the DAT strategy, age, CKD, and anemia were strong predictors of an increased risk of NACE, whereas the use of DOAC instead of VKA was a predictor of reduced risk. Efficacy and safety of clopidogrel-based vs. aspirin-based DAT. The comparable efficacy and safety observed in our analysis is consistent with the other evidence currently available (13, 14). In the retrospective, observational study conducted in South Korea using data from the National Health Insurance Service claims, 9,157 AF patients who received clopidogrel-based or aspirin-based DAT following PCI were identified (13). After 1:1 propensity score matching, two groups of 2,882 patients each were established and compared (13). No significant differences were found between the two groups as regards major adverse cardiac events (a composite of cardiovascular death, MI, ischemic stroke, or systemic thromboembolism), ischemic endpoints, major bleeding, and NACE (all-cause death, MI, stroke, systemic thromboembolism, and major bleeding) (13). In the subgroup analysis of the STOPDAPT-3 trial (Short and Optimal Duration of Dual Antiplatelet Therapy-3) which compared 1-month dual antiplatelet therapy followed by aspirin monotherapy with 1-month prasugrel monotherapy followed by clopidogrel monotherapy, patients were stratified by OAC at discharge and compared as regards the occurrence between 30 days and 1 year of the co-primary cardiovascular (a composite of cardiovascular death, MI, definite stent thrombosis, or ischemic stroke), and bleeding (BARC 3 or 5) endpoints (14). Regardless of OAC therapy, which was prescribed for various indications, mainly including arrhythmia, left ventricular thrombus, venous thromboembolism, and stroke, no differences were observed between clopidogrel and aspirin in the occurrence of the co-primary cardiovascular and bleeding endpoints (14). The above and our data taken together may appear to conflict with the accumulating literature showing that clopidogrel is associated with a superior net clinical benefit compared to aspirin when used as monotherapy in the secondary prevention of patients who underwent PCI, however without indication for OAC (19, 20). Nonetheless, such superior net clinical benefit appears to be essentially driven by a consistent and significant reduction in bleeding events with an inconstant favorable effect on ischemic events, including either MI or stroke (19, 20). When pooling together all the available data on patients who underwent PCI as it was done in a recent meta-analysis of 7 studies that included 20,360 patients, the superior overall efficacy of clopidogrel over aspirin was found to be driven by a trend, however not significant for any variable, of reduction of MI, cardiac death, and stent thrombosis (21). No significant differences in the occurrence of major bleeding were either observed (21). In accordance, in the recent ESC Guidelines on the management of chronic coronary syndromes clopidogrel is placed on the same level as aspirin in patients with previous PCI, being recommended as an alternative and not in preference to it (22). The mechanism through which clopidogrel inhibits platelet aggregation may actually explain the superior efficacy on ischemic endpoints reported in various observations in patients with coronary heart disease (19–21, 23). The blockade of the P2Y12 receptor that occurs downstream of the intervention of various agonists of platelet aggregation, such as von Willebrand factor, collagen, thromboxane A2 and thrombin, can determine an antithrombotic effect superior to that obtained from the inhibition of thromboxane A2 alone induced by aspirin (24). It is possible that this effect of clopidogrel compared to aspirin is dampened in the context of the upstream inhibition of the generation and activity of thrombin, which is the most potent among the various promoters of platelet aggregation (24), as occurs in the context of chronic OAC. This could be at the basis of the lack of differences in the occurrence of MACCE between the clopidogrel-based and aspirin-based DAT observed in our analysis (Table 2 ). Similarly, the inhibition of the generation and activity of thrombin may have equalized upstream the potential differences of clopidogrel and aspirin on the incidence of bleeding events which therefore resulted similar in the two groups (Table 2 ). Regardless of the underlying mechanism, the net effect observed in our analysis was that of a survival free from NACE comparable between clopidogrel-based and aspirin-based DAT, both overall and at the one-year landmark analysis (Figg. 3A and 3B). Predictors of adverse events. Another result of our analysis was that also in the OAC population the predictors of subsequent adverse events following PCI appear to be essentially the same as in the general population, namely older age, CKD, anemia, CHA 2 D S -VASc and HAS-BLED scores, and number of stents implanted (25, 26), irrespective of whether the DAT regimen is clopidogrel-based or aspirin-based (Table 3 ). Particular attention must therefore be paid to OAC patients with the above characteristics when undergoing PCI, as had already been suggested by previous observations from the VKA era in AF patients (27–30). Of further note, is that irrespective of the either clopidogrel-based or aspirin-based DAT regimen, the superiority of DOAC vs. VKA on the occurrence of NACE, widely demonstrated in the general population with AF, (31) was also confirmed in our analysis (Table 3 ), thereby further supporting current Guidelines recommendations (7). Limitations. While remarking that our analysis is strengthened by both the fact that is the first reporting on the effects of a clopidogrel-based vs. aspirin-based DAT regimen in a Western population on OAC undergoing PCI and is representative of current practice in a real-world setting, its several limitations need however to be acknowledged. First, the observational design of the study makes it subject to the inherent constraints of this methodology. Second, the indications for and regimen of OAC were various therefore determining increased heterogeneity of the study population. Nevertheless, our analysis accounted for several confounding factors through appropriate adjustments. In line with the largely comparable baseline characteristics in the aspirin- and clopidogrel-based DAT, as well as the consistency of the findings in multivariable Cox models adjusting for major prognostic factors, a propensity score–matched analysis was not performed, as it would have further reduced the effective sample size without being expected to modify the neutral association between the two DAT regimens and clinical outcomes. Third, no information was available regarding the PCI complexity nor the doses of DOAC use which both may impact on the overall efficacy and safety of any DAT regimen. Finally, although statistically not significant, clopidogrel might have a numerical advantage since more patients had been involved in the clopidogrel-based DAT group. Thus, the generalizability of our results should be interpreted with caution and further validated through dedicated randomized controlled trials. CONCLUSIONS In the population of consecutive patients on OAC for various indications undergoing PCI who were enrolled in the Italian, multi-center, prospective PERSEO registry, no significant difference in the occurrence of NACE was observed between clopidogrel-based vs. aspirin-based DAT following an initial course of TAT. While established predictors of adverse events following PCI, such as advanced age, CKD, anemia, CHA 2 D S -VASc and HAS-BLED scores, and number of stents implanted, were confirmed also in this OAC population, no clinical or procedural variables were identified to guide the selection of clopidogrel vs. aspirin in DAT combination. Besides the demonstration of phenotypic or genotypic non-responsiveness to clopidogrel, or the need for concomitant administration of PPI, which regardless of the agent has been recently shown to decrease the efficacy of clopidogrel monotherapy following PCI (32), the choice between clopidogrel-based vs. aspirin based DAT should be left at present at the discretion of the attending physician. Declarations FUNDING This work was not supported by any sponsor or funder. DATA AVAILABILITY Anonymized raw data is available from authors upon reasonable request. DECLARATION CONFLICTS OF INTEREST. A.R. declares Lecture fees from and/or consulting for Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer BMS outside the submitted work. G.A. declares personal fees and non-financial support from Daiichi Sankyo, Amgen, and Boehringer Ingelheim, and personal fees from AstraZeneca, Chiesi, and Sanofi, outside the submitted work. A.S. declares consulting for Novo Nordisk, and Daiichi Sankyo outside the submitted work. The other authors declare no conflict of interest. Author Contribution Conceptualization, A.R.; methodology, A.R., G.P. , and A.S.; validation, A.R., and A.S; formal analysis, G.P.; data curation, S.D.R., P.C., C.M., B.C., M.C., V.P., G.A., and A.S.; writing, original draft preparation, A.R, G.A., and G.P.; writing, review and editing, A.R., G.P., and A.S. All authors have read and agreed to the published version of the manuscript. References Dewilde WJ, Oirbans T, Verheugt FW, Kelder JC, De Smet BJ, Herrman JP, Adriaenssens T, Vrolix M, Heestermans AA, Vis MM, Tijsen JG, van 't Hof AW, ten Berg JM, WOEST study investigators (2013) Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 381:1107–1115. 10.1016/S0140-6736(12)62177-1 Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, Birmingham M, Ianus J, Burton P, van Eickels M, Korjian S, Daaboul Y, Lip GY, Cohen M, Husted S, Peterson ED, Fox KA (2016) Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med 375:2423–2434. 10.1056/NEJMoa1611594 Cannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, Maeng M, Merkely B, Zeymer U, Gropper S, Nordaby M, Kleine E, Harper R, Manassie J, Januzzi JL, Ten Berg JM, Steg PG, Hohnloser SH, RE-DUAL PCI Steering Committee and Investigators (2017) Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med 377:1513–1524. 10.1056/NEJMoa1708454 Lopes RD, Heizer G, Aronson R, Vora AN, Massaro T, Mehran R, Goodman SG, Windecker S, Darius H, Li J, Averkov O, Bahit MC, Berwanger O, Budaj A, Hijazi Z, Parkhomenko A, Sinnaeve P, Storey RF, Thiele H, Vinereanu D, Granger CB, Alexander JH, AUGUSTUS Investigators (2019) Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. N Engl J Med 380:1509–1524. 10.1056/NEJMoa1817083 Epub 2019 Mar 17. PMID: 30883055 Vranckx P, Valgimigli M, Eckardt L, Tijssen J, Lewalter T, Gargiulo G, Batushkin V, Campo G, Lysak Z, Vakaliuk I, Milewski K, Laeis P, Reimitz PE, Smolnik R, Zierhut W, Goette A (2019) Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial. Lancet 394(10206):1335–1343. 10.1016/S0140-6736(19)31872-0 Kumbhani DJ, Cannon CP, Beavers CJ, Bhatt DL, Cuker A, Gluckman TJ, Marine JE, Mehran R, Messe SR, Patel NS, Peterson BE, Rosenfield K, Spinler SA, Thourani VH (2021) 2020 ACC Expert Consensus Decision Pathway for Anticoagulant and Antiplatelet Therapy in Patients With Atrial Fibrillation or Venous Thromboembolism Undergoing Percutaneous Coronary Intervention or With Atherosclerotic Cardiovascular Disease: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 77:629–658. 10.1016/j.jacc.2020.09.011 Van Gelder IC, Rienstra M, Bunting KV, Casado-Arroyo R, Caso V, Crijns HJGM, De Potter TJR, Dwight J, Guasti L, Hanke T, Jaarsma T, Lettino M, Løchen ML, Lumbers RT, Maesen B, Mølgaard I, Rosano GMC, Sanders P, Schnabel RB, Suwalski P, Svennberg E, Tamargo J, Tica O, Traykov V, Tzeis S, Kotecha D, ESC Scientific Document Group (2024) 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 45:3314–3414. 10.1093/eurheartj/ehae176 Praz F, Borger MA, Lanz J, Marin-Cuartas M, Abreu A, Adamo M, Ajmone Marsan N, Barili F, Bonaros N, Cosyns B, De Paulis R, Gamra H, Jahangiri M, Jeppsson A, Klautz RJM, Mores B, Pérez-David E, Pöss J, Prendergast BD, Rocca B, Rossello X, Suzuki M, Thiele H, Tribouilloy CM, Wojakowski W, ESC/EACTS Scientific Document Group (2025) 2025 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 46:4635–4736. 10.1093/eurheartj/ehaf194 Sofi F, Marcucci R, Gori AM, Giusti B, Abbate R, Gensini GF (2010) Clopidogrel non-responsiveness and risk of cardiovascular morbidity. updated meta-analysis Thromb Haemost 103:841–848. 10.1160/TH09-06-0418 Lau WC, Waskell LA, Watkins PB, Neer CJ, Horowitz K, Hopp AS, Tait AR, Carville DG, Guyer KE, Bates ER (2003) Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation 107:32–37. 10.1161/01.cir.0000047060.60595.cc Martini L, Lisi M, Pompei G, Arioti M, Bendandi F, Henein MY, Cameli M, Rubboli A (2025) Antiplatelet Therapy in Atrial Fibrillation Patients on Direct Oral Anticoagulants Undergoing Percutaneous Coronary Intervention: Which and How. J Clin Med 14:6331. 10.3390/jcm14176331 Kim HK, Tantry US, Smith SC Jr, Jeong MH, Park SJ, Kim MH, Lim DS, Shin ES, Park DW, Huo Y, Chen SL, Bo Z, Goto S, Kimura T, Yasuda S, Chen WJ, Chan M, Aradi D, Geisler T, Gorog DA, Sibbing D, Lip GYH, Angiolillo DJ, Gurbel PA, Jeong YH (2021) The East Asian Paradox: An Updated Position Statement on the Challenges to the Current Antithrombotic Strategy in Patients with Cardiovascular Disease. Thromb Haemost 121:422–432. 10.1055/s-0040-1718729 Kim S, Park S, Kim H, Aung N, Kim SH, Chang K, Choi Y (2025) Clinical outcomes with the use of aspirin vs. clopidogrel as a combination therapy with direct oral anticoagulant after coronary stent implantation in patients with atrial fibrillation. Eur Heart J Cardiovasc Pharmacother 11:532–539. 10.1093/ehjcvp/pvaf043 Natsuaki M, Watanabe H, Morimoto T, Yamamoto K, Obayashi Y, Nishikawa R, Kimura T, Ando K, Suwa S, Isawa T, Takenaka H, Ishikawa T, Tamura T, Kawahatsu K, Hayashi F, Akao M, Serikawa T, Mori H, Kawamura T, Hagikura A, Shibata N, Ono K, Kimura T (2025) Aspirin Versus Clopidogrel Beyond 1 Month After PCI in Patients With Oral Anticoagulation. Circ Cardiovasc Interv 18:e015495. 10.1161/CIRCINTERVENTIONS.125.015495 Sciahbasi A, Gargiulo G, Talarico GP, Cesaro A, Zilio F, De Rosa S, Talanas G, Tebaldi M, Andò G, Rigattieri S, Misuraca L, Cortese B, Imperadore F, Lucci V, Guiducci V, Renda G, Zezza L, Versaci F, Giannico MB, Caruso M, Spaccarotella C, Calabrò P, Esposito G, Tarantini G, Musumeci G, Rubboli A (2022) Design of the PERSEO Registry on the management of patients treated with oral anticoagulants and coronary stent. J Cardiovasc Med (Hagerstown) 23:738–743. 10.2459/JCM.0000000000001372 Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW, Academic Research Consortium (2007) Clinical end points in coronary stent trials: a case for standardized definitions.Circulation 115(17):2344-51. 10.1161/CIRCULATIONAHA.106.685313 Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H (2011) Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 123:2736–2747. 10.1161 CIRCULATIONAHA.110.009449 Sciahbasi A, De Rosa S, Gargiulo G, Giacoppo D, Calabrò P, Talarico GP, Zilio F, Talanas G, Tebaldi M, Andò G, Rigattieri S, Misuraca L, Cortese B, Musuraca G, Lucci V, Guiducci V, Renda G, Zezza L, Versaci F, Giannico MB, Caruso M, Fischetti D, Colletta M, Santarelli A, Larosa C, Iannone A, Esposito G, Tarantini G, Musumeci G, Rubboli A (2024) Management of Patients Treated With Oral Anticoagulant Therapy Undergoing Percutaneous Coronary Intervention With Stent Implantation: The PERSEO Registry. J Cardiovasc Pharmacol 84:457–467. 10.1097/FJC.0000000000001607 Koo BK, Kang J, Park KW, Rhee TM, Yang HM, Won KB, Rha SW, Bae JW, Lee NH, Hur SH, Yoon J, Park TH, Kim BS, Lim SW, Cho YH, Jeon DW, Kim SH, Han JK, Shin ES, Kim HS, HOST-EXAM investigators (2021) Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial. Lancet 397:2487–2496. 10.1016/S0140-6736(21)01063-1 Choi KH, Park YH, Lee JY, Jeong JO, Kim CJ, Yun KH, Lee HC, Chang K, Park MW, Bae JW, Doh JH, Cho BR, Kim HY, Kim W, Kim U, Rha SW, Hong YJ, Lee HJ, Ahn SG, Kim DI, Cho JH, Her SH, Jeon DS, Han SH, Lee JB, Lee CW, Kang D, Lee JM, Park TK, Yang JH, Lee SY, Choi SH, Gwon HC, Song YB, Hahn JY, SMART-CHOICE 3 investigators (2025) Efficacy and safety of clopidogrel versus aspirin monotherapy in patients at high risk of subsequent cardiovascular event after percutaneous coronary intervention (SMART-CHOICE 3): a randomised, open-label, multicentre trial. Lancet 405:1252–1263. 10.1016/S0140-6736(25)00449-0 Wani SA, Naveed MA, Azeem B, Ashraf S, Ali A, Ali T, Fatima F, Shah M, Neppala S, Ahmed R (2025) Comparative outcomes of clopidogrel vs aspirin monotherapy in post-PCI patients: An updated systematic review and meta-analysis. Cardiovasc Revasc Med 80:122–130. 10.1016/j.carrev.2025.06.006 Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S, ESC Scientific Document Group (2024). 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. ;45(36):3415–3537. 10.1093/eurheartj/ehae177 . PMID: 39210710 Valgimigli M, Choi KH, Giacoppo D, Gragnano F, Kimura T, Watanabe H, Kim HS, Kang J, Park KW, Pettersen AÅ, Woodward M, Bhatt DL, Calabrò P, Angiolillo DJ, Mehran R, Song YB, Hahn JY (2025) Clopidogrel versus aspirin for secondary prevention of coronary artery disease: a systematic review and individual patient data meta-analysis. Lancet 406:1091–1102. 10.1016S0140-6736(25)01562-4 Dorsam RT, Kunapuli SP (2004) Central role of the P2Y12 receptor in platelet activation. J Clin Invest 113:340–345. 10.1172/JCI20986 Lee PC, Kini AS, Ahsan C, Fisher E, Sharma SK (2004) Anemia is an independent predictor of mortality after percutaneous coronary intervention. J Am Coll Cardiol 44(3):541–546. 10.1016/j.jacc.2004.04.047 Deng W, Wang D, Wan Y, Lai S, Ding Y, Wang X (2024) Prediction models for major adverse cardiovascular events after percutaneous coronary intervention: a systematic review. Front Cardiovasc Med 10:1287434. 10.3389/fcvm.2023.1287434 Puurunen MK, Kiviniemi T, Schlitt A, Rubboli A, Dietrich B, Karjalainen P, Nyman K, Niemelä M, Lip GY, Airaksinen KE (2014) CHADS2, CHA2DS2-VASc and HAS-BLED as predictors of outcome in patients with atrial fibrillation undergoing percutaneous coronary intervention. Thromb Res 133:560–566. 10.1016/j.thromres.2014.01.007 Puurunen M, Kiviniemi T, Nammas W, Schlitt A, Rubboli A, Nyman K, Karjalainen P, Kirchhof P, Lip GY, Airaksinen JK (2014) Impact of anaemia on clinical outcome in patients with atrial fibrillation undergoing percutaneous coronary intervention: insights from the AFCAS registry. BMJ Open 4:e004700. 10.1136/bmjopen-2013-004700 Lahtela HM, Kiviniemi TO, Puurunen MK, Schlitt A, Rubboli A, Ylitalo A, Valencia J, Lip GY, Airaksinen KE (2015) Renal Impairment and Prognosis of Patients with Atrial Fibrillation Undergoing Coronary Intervention - The AFCAS Trial. PLoS ONE 10:e0128492. 10.1371/journal.pone.0128492 Lahtela HM, Bah A, Kiviniemi T, Nammas W, Schlitt A, Rubboli A, Karjalainen PP, Proietti M, Hartikainen JEK, Lip GYH, Airaksinen KEJ (2017) Outcome of octogenarians with atrial fibrillation undergoing percutaneous coronary intervention: insights from the AFCAS registry. Clin Cardiol 40:1264–1270. 10.1002/clc.22821 Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM (2014) Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 383(9921):955–962. 10.1016/S0140-6736(13)62343-0 Nishikura T, Yamamoto K, Wakabayashi K, Natsuaki M, Watanabe H, Morimoto T, Obayashi Y, Nishikawa R, Kimura T, Ando K, Suwa S, Isawa T, Takenaka H, Ishikawa T, Onishi Y, Hibi K, Kawai K, Murakami T, Takasaki A, Higashitani N, Nakano M, Ono K, Kimura T, STOPDAPT-3 investigators (2025) Effect of Proton Pump Inhibitors in Patients Undergoing Percutaneous Coronary Intervention With Aspirin-Free Strategy. JACC Asia Nov 13:S2772-3747(25)00542-3. 10.1016/j.jacasi.2025.09.015 Tables Table 1. Baseline characteristics. Clopidogrel-based DAT (N=769 Aspirin-based DAT N=220 p-value Age, median [IQR] 76 [70,81] 74 [68,81] 0.033 Male, n (%) 556 (72.3) 166 (75.5) 0.353 BMI, median IQR] 26.5 [24.3, 29.4] 26.9 [24.5, 29.3] 0.956 Diabetes, n (%) 271 (35.2) 76 (34.6) 0.849 Hypertension, n (%) 672 (87.4) 188 (85.5) 0.453 Smoking habits, n (%) 279 (36.3) 89 (40.5) 0.259 eGFR (ml/min 1.73 m 2 ), median 68.9 [52.4, 86.7] 70.1 [54.5, 86.5] 0.523 LVEF, median [IQR] 50 [38, 55] 48 [38, 55] 0.824 CHA 2 DS 2 VASc score, median [IQR] 4 [3, 5] 4 [3, 5] 0.048 HAS-BLED score, median [IQR] 4 [3, 4] 3 [3, 4] 0.061 CHARLSON score, median [IQR] 2 [1, 3] 2 [1, 4] 0.350 DOAC use, n (%) 664 (86.4) 181 (82.3) 0.120 PPI use, n (%) 721 (93.8) 203 (92.3) 0.433 M edical history , n (%) Previous MI 176 (22.9) 59 (26.8) 0.227 Previous PCI 190 (24.7) 67 (30.5) 0.087 Previous CABG 59 (7.7) 22 (10) 0.267 Previous bleeding 48 (6.2) 11 (5) 0.493 Previous stroke 1 (0.1) 2 (0.9) 0.064 Previous TIA 92 (12) 20 (9.1) 0.236 PAD 168 (21.8) 59 (26.8) 0.122 CKD 274 (35.6) 73 (33.2) 0.502 HF 240 (31.2) 79 (35.9) 0.189 COPD 108 (14) 33 (15) 0.721 Liver disease 23 (3) 9 (4.1) 0.441 Alcohol 6 (0.8) 3 (1.4) 0.422 Anaemia 83 (10.8) 17 (7.7) 0.183 Peptic ulcer 15 (2) 2 (0.9) 0.295 Cancer 57 (7.4) 13 (5.9) 0.443 Clinical presentation, n (%) ACS HF Arrhythmia CCS Syncope Heart valve disease 477 (62) 113 (14.7) 26 (3.4) 138 (17.9) 4 (0.5) 3 (0.4) 134 (60.9) 31 (14.1) 12 (5.5) 42 (19.1) 0 (0.0) 1 (0.5) 0.474 Indication for OAC , n (%) AF VTE Mechanical heart valve LV thrombus Others 686 (89.2) 34 (4.4) 16 (2.1) 19 (2.5) 14 (1.8) 193 (87.7) 11 (5) 6 (2.7) 8 (3.6) 2 (0.9) 0.471 Procedural characteristics , n (%) Radial access 678 (88.2) 205 (93.2) 0.034 N. of implanted stents 1 2 3 >3 442 (57.5) 209 (27.2) 72 (9.4) 46 (6) 125 (56.8) 65 (29.6) 21 (9.6) 9 (4.1) 0.662 ACS: acute coronary syndrome; DAT: double antithrombotic therapy; IQR: interquartile range; BMI: body mass index; MI: myocardial infarction; PCI: percutaneous coronary intervention; CABG: coronary artery bypass grafting; TIA: transient ischaemic attack; PAD: peripheral artery disease; CKD: chronic kidney disease; eGFR: estimated glomerular filtration rate; HF: heart failure; CCS: chronic coronary syndrome; LV: left ventricular; LVEF: left ventricular ejection fraction; COPD: chronic obstructive pulmonary disease; OAC: oral anticoagulant; AF: atrial fibrillation; PE: pulmonary embolism; VTE: venous thromboembolism; DOAC: direct oral anticoagulant; PPI: proton-pump inhibitor. Table 2. Clinical outcomes. Adverse clinical events Clopidogrel -based DAT N=769 Aspirin-based DAT N=220 p-value Primary endpoint , n (%) NACE 147 (19.1) 44 (20) 0.770 Secondary endpoints, n (%) MACCE 79 (10.3) 19 (8.6) 0.474 All-cause death 66 (8.6) 20 (9.1) 0.813 Cardiac death 14 (1.8) 8 (3.6) 0.107 Stroke/TIA 9 (1.2) 2 (0.9) 0.745 Non-fatal MI 17 (0.1) 2 (0.9) 0.215 Stent thrombosis 6 (0.8) 1 (0.5) 0.611 TVR 11 (1.4) 1 (0.5) 0.244 Major bleedings (BARC 3-5) 17 (2.2) 3 (1.4) 0.431 Clinically relevant bleedings (BARC 2, 3, 5) 57 (7.4) 16 (7.3) 0.944 DAT: double antithrombotic therapy; NACE: net adverse clinical events; MACCE: major adverse cardiac/cerebral events; TIA: transient ischemic attack; MI: myocardial infarction; TVR: target vessel revascularization. Table 3. Cox regression analysis for NACE at median follow-up time (12.3 months) including both univariable and multivariable analysis. Variable HR ( 95% CI ) p-value HR multivariable analysis p-value Clopidogrel- vs. aspirin-based DAT 1.06 (0.75, 1.48) 0.756 Age 1.04 (1.02, 1.05) <0.001 1.02 (1.00, 1.04) 0.027 Sex 0.89 (0.65,1.21) 0.463 BMI 0.97 (0.93, 1.00) 0.062 Previous MI 0.95 (0.68, 1.33) 0.770 Previous bleeding 1.57 (0.94, 2.62) 0.086 Previous stroke/TIA 0.67 (0.40, 1.14) 0.139 CKD 1.82 (1.37, 2.42) <0.001 1.49 (1.08, 2.04) 0.014 Anaemia 2 (1.37, 2.91) <0.001 1.62 (1.10, 2.41) 0.016 Cancer 1.58 (0.98, 2.53) 0.059 CHA2DS2-VASc 1.21 (1.10, 1.32) 6 months 1.03 (0.71, 1.50) 0.888 DOAC vs. VKA 0.67 (0.47, 0.95) 0.024 0.69 (0.48, 1.00) 0.047 NACE: net adverse clinical events; HR: hazard ratio; CI: confidence interval; DAT:double antithrombotic therapy; BMI: body mass index; MI: myocardial infarction; TIA: transient ischemic attack; CKD: chronic kidney disease; DOAC: direct oral anticoagulant; VKA: vitamin K-antagonist. Table 4. Univariable and multivariable analysis for clinical adverse events according to clopidogrel-based vs. aspirin-based DAT. Endpoint HR (95% CI) p-value HR multivariable (adjusted for age, CKD, anaemia, number of stents, type of OAC) p-value NACE 1.06 (0.75, 1.48) 0.756 0.98 (0.70, 1.38) 0.923 MACCE 1.42 (0.86, 2.35) 0.172 1.27 (0.76, 2.12) 0.359 All-cause death 1.14 (0.69, 1.89) 0.608 0.99 (0.60, 1.66) 0.984 Cardiac death 0.56 (0.23, 1.34) 0.190 0.46 (0.19, 1.13) 0.090 Stroke/TIA 1.37 (0.29, 6.36) 0.690 1.28 (0.27, 5.98) 0.753 Non-fatal MI 2.59 (0.60, 11.23) 0.204 2.26 (0.52, 9.85) 0.279 BARC 2-5 1.13 (0.65, 1.96) 0.679 1.03 (0.59, 1.81) 0.913 BARC 3-5 1.85 (0.54, 6.36) 0.326 1.60 (0.46, 5.55) 0.910 DAT: double antithrombotic therapy; HR: hazard ratio; CI: confidence interval; CKD: chronic kidney disease; NACE: net adverse clinical events; MACCE: major adverse cardiac/cerebral events; CV: cardiovascular; TIA: transient ischemic attack; MI: myocardial infarction; Additional Declarations No competing interests reported. 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11:59:04","extension":"html","order_by":20,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":179781,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8574706/v1/4782af94ed58150c9d13dfa2.html"},{"id":100401520,"identity":"512079e2-a237-4011-a57f-d53f0724c92a","added_by":"auto","created_at":"2026-01-16 11:59:04","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":411386,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the study. DAT: double antithrombotic therapy.\u003c/p\u003e","description":"","filename":"Figure1.tiff.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8574706/v1/4ce88867469252a3f9671eab.jpg"},{"id":100402646,"identity":"8b1f4c5d-b471-42dc-bcb9-16b8fdde8888","added_by":"auto","created_at":"2026-01-16 12:00:27","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":287248,"visible":true,"origin":"","legend":"\u003cp\u003eMultivariable Cox regression analysis for net adverse cardiac events (NACE) at median follow-up time among patients receiving double antithrombotic therapy (DAT). CKD: chronic kidney disease; DOAC: direct oral anticoagulant.\u003c/p\u003e","description":"","filename":"Figure2.tiff.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8574706/v1/a7fe781d43963076cb5dd8e1.jpg"},{"id":100402500,"identity":"effb729e-31ff-4b20-92b3-6ac03fece640","added_by":"auto","created_at":"2026-01-16 12:00:17","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":967936,"visible":true,"origin":"","legend":"\u003cp\u003eA) Kaplan-Meier curves for net adverse cardiac events (NACE)among patients stratified according to double antithrombotic therapy (DAT). PCI: percutaneous coronary intervention. B) Kaplan-Meier curves for et adverse cardiac events (NACE) at 1-year follow-up among patients stratified according to double antithrombotic therapy (DAT). PCI: percutaneous coronary intervention.\u003c/p\u003e","description":"","filename":"Figure3A.tiff.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8574706/v1/228571581509aba370211876.jpg"},{"id":107927728,"identity":"cbb540a2-b149-480e-b40c-5bc403dc6cb1","added_by":"auto","created_at":"2026-04-27 16:02:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2092702,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8574706/v1/56461349-b117-48ec-9629-ac6b010a0695.pdf"},{"id":100402345,"identity":"1d5199ba-40da-48e5-9fdd-c4fc168fe6e9","added_by":"auto","created_at":"2026-01-16 12:00:02","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1200253,"visible":true,"origin":"","legend":"","description":"","filename":"graphicalabstract.png","url":"https://assets-eu.researchsquare.com/files/rs-8574706/v1/c92e21b1b744fcf5318b9d7e.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eClopidogrel-Based vs. Aspirin-Based Double Antithrombotic Therapy Following Percutaneous Coronary Intervention with Stent in Patients on Oral Anticoagulation. A Post-Hoc Analysis of the Perseo Registry\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eBased on the design of the five randomized clinical trials WOEST (1), PIONEER AF-PCI (2), RE-DUAL PCI (3), AUGUSTUS (4), and ENTRUST-AF PCI (5), which investigated the optimal antithrombotic therapy in patients on oral anticoagulation (OAC), mostly for atrial fibrillation (AF), undergoing percutaneous coronary intervention with stent (PCI), clopidogrel should be the preferred antiplatelet agent to be given in conjunction with OAC in double antithrombotic therapy (DAT) following an initial course of triple antithrombotic therapy (TAT) of OAC, clopidogrel, and aspirin (6\u0026ndash;8). Owing to the potential for clopidogrel non-responsiveness (9), as well as for its pharmacological interactions with drugs commonly used in patients with coronary heart disease, such as atorvastatin (10), which may both hamper its antiplatelet effect, exploring whether an aspirin-based DAT may instead be an option appears valuable (11). Two recent analyses carried out in East Asian patients, whose susceptibility to both thrombosis and bleeding is known to be different from that of Caucasian (12), reported no significant differences either on efficacy or safety when aspirin is given instead of clopidogrel in DAT following PCI in patients on OAC (13, 14). Nonetheless, additional evidence would be of importance to further clarify this issue.\u003c/p\u003e \u003cp\u003e With this aim, we performed a post-hoc analysis of the Italian, multi-center, prospective PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) registry (15), where patients on OAC undergoing PCI were enrolled, to compare the clinical outcomes of a clopidogrel-based vs. an aspirin-based DAT regimen.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cb\u003eStudy design and clinical endpoints.\u003c/b\u003e The multi-center, prospective, observational PERSEO registry (ClinicalTrials.gov Identifier: NCT03392948) was conducted at twenty-five centers in Italy, and enrolled consecutive patients on OAC for various indications, including AF, venous thromboembolism, left ventricular thrombus, and mechanical heart valves, undergoing PCI (15). Age\u0026thinsp;\u0026lt;\u0026thinsp;18 years and lack of informed signed consent were the only exclusion criteria (15). In accordance with the observational design of the study, the pharmacological and interventional management before, during, and after PCI was entirely at the operator\u0026rsquo;s discretion (15). All clinical variables were recorded in an electronic Case Report Form (eCRF) following anonymization of patient details by assigning a unique study identifier (15). An independent dedicated society (Advice Pharma Group Srl, Milan, Italy) provided the eCRF and stored the data (15). The PERSEO registry was endorsed by the Italian Society of Interventional Cardiology (SICI-GISE) and was approved by the Ethic Committees of each participating center.\u003c/p\u003e \u003cp\u003eFor the purpose of this \u003cem\u003epost-hoc\u003c/em\u003e analysis, patients who received clopidogrel and aspirin in the context of DAT following the initial course of TAT, were identified and compared as regards the occurrence of net adverse clinical events (NACE), including major adverse cardiac/cerebral events (MACCE) and major bleeding (primary outcome). MACCE included urgent and unplanned target vessel revascularization (TVR), non-fatal myocardial infarction (MI), stent thrombosis, non-fatal stroke/transient ischemic attack (TIA), and all-cause death. Secondary outcomes, including MACCE, all-cause death, cardiac death, non-fatal MI, non-fatal stroke/TIA, TVR, and major and clinically relevant bleeding were also compared. Stent thrombosis was defined according to the Academic Research Consortium (ARC) definition as definite, probable, and possible (16). Bleeding events were classified according to the Bleeding Academic Research Consortium (BARC) criteria as major (BARC 3 and 5), and clinically relevant (BARC 2\u0026ndash;5) (17).\u003c/p\u003e \u003cp\u003eBy performing a landmark analysis with the date of TAT discontinuation identified as baseline, the median follow-up time was calculated based on the duration of DAT. Patients whose DAT regimen was modified during follow-up were included, however only the first DAT regimen was considered. Follow-up for these patients was censored at the time the initial DAT regimen was discontinued to switch to an alternative regimen. Patients who died in hospital while receiving TAT were excluded from the analysis as they did not receive any DAT.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical analysis.\u003c/b\u003e Categorical baseline data are presented as numbers and percentage (n, %) and analyzed with Chi-squared Monte-Carlo test. Continuous data were first tested for normality using the Shapiro-Wilk test, for which P\u0026thinsp;\u0026gt;\u0026thinsp;0.05 was considered as normally distributed and P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 as non-normal. Normally distributed data are presented as mean and standard deviation (SD), and were validated with Levene\u0026rsquo;s test for equality of variance before analyzing with the independent T-test. Non-normally distributed data are presented as median and interquartile range (IQR), and were analyzed by the Mann-Whitney U Monte-Carlo test. To analyze the impact of independent variables on follow-up outcomes, Kaplan-Meier analysis was conducted along with Log-rank test to determine difference between groups. Kaplan Meier survival analysis was performed for the primary composite outcome of NACE, for which time-to-first event was designated as the disease-free survival time in years. Cox regression was further performed separately for each component of the primary composite outcome, yielding hazard ratios (HR) with 95% confidence intervals (CI). Multivariable models were constructed to adjust for potential pre-specified confounding factors resulting significant at univariable analysis. All statistical analyses were performed on the Statistical Package for the Social Sciences (SPSS V.29, IBM Corporation). Significance was predetermined at the level two-tailed p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eOf the 1,234 patients enrolled in the PERSEO registry (18), six who experienced in-hospital death during TAT and 239 who never received DAT, were excluded from the analysis. Therefore, the final study population consisted of 989 patients who initiated DAT after an initial period of TAT, of whom 769 (78%) received clopidogrel and 220 (22%) received aspirin (Fig. 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eBaseline characteristics\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;(Table 1).\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eNo differences were observed between the two groups receiving clopidogrel-based and aspirin-based DAT, with the exception of median age which was significantly higher in the clopidogrel group. The indications for both PCI and OAC were comparable, with acute coronary syndrome (ACS) and AF respectively, being the most common. The proportions of use of both direct oral anticoagulants (DOAC) and proton-pump inhibitors (PPI) were also comparable in the two groups. The CHA₂DS₂-VASc score, which was calculated as well as the HAS-BLED score only in patients with AF, was significantly higher in the clopidogrel group. The radial approach was used significantly less in the clopidogrel group. No differences were observed in the number of stents implanted, with most patients receiving one or two stents.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePrimary and secondary outcomes (Table 2)\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eAt a median follow-up of 12.3 months, the primary outcome of NACE was similar in the clopidogrel-based and aspirin-based DAT groups. Secondary outcomes of MACCE, all-cause death, cardiac death, non-fatal MI, stent thrombosis, non-fatal stroke/TIA, TVR, and major and clinically relevant bleeding were also comparable. Bleeding events, including major bleeding and clinically relevant bleeding, were similar in both groups. Overall, no significant differences were observed between clopidogrel-based and aspirin-based DAT regimens across primary and secondary outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eUnivariable, multivariable, and survival analysis.\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eAt the univariable Cox regression analysis, clopidogrel-based vs. aspirin-based DAT was not associated with a significant difference in the risk of NACE, and this remained non-significant after adjustment for age, chronic kidney disease (CKD), anaemia, number of implanted stents, and type of OAC, i.e., vitamin K antagonist (VKA) vs. direct oral anticoagulants (DOAC) (Table 3). Age emerged as a significant predictor of increased risk of NACE, and this association persisted in multivariable analysis (Table 3, Fig. 2). CKD and anaemia were also strong predictors of increased risk of NACE in both univariable and multivariable models (Table 3, Fig. 2), as well as was the number of stents implanted (Table 3, Fig. 2). The use of DOAC rather than VKA was associated with a reduced risk of NACE at both univariable and multivariable analysis (Table 3, Fig. 2). Both CHA\u003csub\u003e2\u003c/sub\u003eDS\u003csub\u003e2\u003c/sub\u003e-VASc and HAS-BLED scores showed a significant association with an increased risk of NACE at univariable analysis, but did not retain significance after adjustment (Table 3, Fig. 2). Clopidogrel-based vs. aspirin-based DAT was not associated with a significant difference in the risk of MACE, all-cause mortality, cardiac death, and stroke/TIA at both unadjusted and adjusted analysis (Table 4). Bleeding outcomes also did not differ between the two treatment strategies (Table 4). Overall, after adjustment for key clinical covariates, no clinical outcome showed a significant difference in risk between clopidogrel-based and aspirin-based DAT (Table 4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt survival analysis, both clopidogrel-based and aspirin-based DAT groups showed a similar risk profile for the cumulative incidence of NACE over the entire duration of DAT (p log-rank= 0.756), with a steady accumulation of events during the initial months of follow-up (Fig. 3A). At the 1-year landmark analysis, the cumulative incidence trajectories of the clopidogrel-based and aspirin-based DAT regimens remained substantially overlapping, with no significant differences between the two groups (p log-rank p=0.552) (Fig. 3B). \u0026nbsp;\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe main findings of this post-hoc analysis of the Italian, multi-center, prospective PERSEO registry, in which a clopidogrel-based vs. an aspirin-based DAT regimen following an initial course of TAT in OAC patients undergoing PCI were compared, are as follows: 1) no significant differences were observed in NACE, nor in either efficacy (MACCE, all-cause death, cardiac death, non-fatal myocardial infarction, stent thrombosis, non-fatal stroke/TIA, and TVR) or safety (major and clinically relevant bleeding) outcomes, 2) NACE-free survival rates were comparable between the two DAT regimens, 3) regardless of the DAT strategy, age, CKD, and anemia were strong predictors of an increased risk of NACE, whereas the use of DOAC instead of VKA was a predictor of reduced risk.\u003c/p\u003e \u003cp\u003e \u003cb\u003eEfficacy and safety of clopidogrel-based vs. aspirin-based DAT.\u003c/b\u003e The comparable efficacy and safety observed in our analysis is consistent with the other evidence currently available (13, 14). In the retrospective, observational study conducted in South Korea using data from the National Health Insurance Service claims, 9,157 AF patients who received clopidogrel-based or aspirin-based DAT following PCI were identified (13). After 1:1 propensity score matching, two groups of 2,882 patients each were established and compared (13). No significant differences were found between the two groups as regards major adverse cardiac events (a composite of cardiovascular death, MI, ischemic stroke, or systemic thromboembolism), ischemic endpoints, major bleeding, and NACE (all-cause death, MI, stroke, systemic thromboembolism, and major bleeding) (13). In the subgroup analysis of the STOPDAPT-3 trial (Short and Optimal Duration of Dual Antiplatelet Therapy-3) which compared 1-month dual antiplatelet therapy followed by aspirin monotherapy with 1-month prasugrel monotherapy followed by clopidogrel monotherapy, patients were stratified by OAC at discharge and compared as regards the occurrence between 30 days and 1 year of the co-primary cardiovascular (a composite of cardiovascular death, MI, definite stent thrombosis, or ischemic stroke), and bleeding (BARC 3 or 5) endpoints (14). Regardless of OAC therapy, which was prescribed for various indications, mainly including arrhythmia, left ventricular thrombus, venous thromboembolism, and stroke, no differences were observed between clopidogrel and aspirin in the occurrence of the co-primary cardiovascular and bleeding endpoints (14).\u003c/p\u003e \u003cp\u003eThe above and our data taken together may appear to conflict with the accumulating literature showing that clopidogrel is associated with a superior net clinical benefit compared to aspirin when used as monotherapy in the secondary prevention of patients who underwent PCI, however without indication for OAC (19, 20). Nonetheless, such superior net clinical benefit appears to be essentially driven by a consistent and significant reduction in bleeding events with an inconstant favorable effect on ischemic events, including either MI or stroke (19, 20). When pooling together all the available data on patients who underwent PCI as it was done in a recent meta-analysis of 7 studies that included 20,360 patients, the superior overall efficacy of clopidogrel over aspirin was found to be driven by a trend, however not significant for any variable, of reduction of MI, cardiac death, and stent thrombosis (21). No significant differences in the occurrence of major bleeding were either observed (21). In accordance, in the recent ESC Guidelines on the management of chronic coronary syndromes clopidogrel is placed on the same level as aspirin in patients with previous PCI, being recommended as an alternative and not in preference to it (22). The mechanism through which clopidogrel inhibits platelet aggregation may actually explain the superior efficacy on ischemic endpoints reported in various observations in patients with coronary heart disease (19\u0026ndash;21, 23). The blockade of the P2Y12 receptor that occurs downstream of the intervention of various agonists of platelet aggregation, such as von Willebrand factor, collagen, thromboxane A2 and thrombin, can determine an antithrombotic effect superior to that obtained from the inhibition of thromboxane A2 alone induced by aspirin (24). It is possible that this effect of clopidogrel compared to aspirin is dampened in the context of the upstream inhibition of the generation and activity of thrombin, which is the most potent among the various promoters of platelet aggregation (24), as occurs in the context of chronic OAC. This could be at the basis of the lack of differences in the occurrence of MACCE between the clopidogrel-based and aspirin-based DAT observed in our analysis (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Similarly, the inhibition of the generation and activity of thrombin may have equalized upstream the potential differences of clopidogrel and aspirin on the incidence of bleeding events which therefore resulted similar in the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Regardless of the underlying mechanism, the net effect observed in our analysis was that of a survival free from NACE comparable between clopidogrel-based and aspirin-based DAT, both overall and at the one-year landmark analysis (Figg. 3A and 3B).\u003c/p\u003e \u003cp\u003e\u003cb\u003ePredictors of adverse events.\u003c/b\u003e Another result of our analysis was that also in the OAC population the predictors of subsequent adverse events following PCI appear to be essentially the same as in the general population, namely older age, CKD, anemia, CHA\u003csub\u003e2\u003c/sub\u003eD\u003csub\u003eS\u003c/sub\u003e-VASc and HAS-BLED scores, and number of stents implanted (25, 26), irrespective of whether the DAT regimen is clopidogrel-based or aspirin-based (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Particular attention must therefore be paid to OAC patients with the above characteristics when undergoing PCI, as had already been suggested by previous observations from the VKA era in AF patients (27\u0026ndash;30). Of further note, is that irrespective of the either clopidogrel-based or aspirin-based DAT regimen, the superiority of DOAC vs. VKA on the occurrence of NACE, widely demonstrated in the general population with AF, (31) was also confirmed in our analysis (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), thereby further supporting current Guidelines recommendations (7).\u003c/p\u003e \u003cp\u003e \u003cb\u003eLimitations.\u003c/b\u003e While remarking that our analysis is strengthened by both the fact that is the first reporting on the effects of a clopidogrel-based vs. aspirin-based DAT regimen in a Western population on OAC undergoing PCI and is representative of current practice in a real-world setting, its several limitations need however to be acknowledged. First, the observational design of the study makes it subject to the inherent constraints of this methodology. Second, the indications for and regimen of OAC were various therefore determining increased heterogeneity of the study population. Nevertheless, our analysis accounted for several confounding factors through appropriate adjustments. In line with the largely comparable baseline characteristics in the aspirin- and clopidogrel-based DAT, as well as the consistency of the findings in multivariable Cox models adjusting for major prognostic factors, a propensity score\u0026ndash;matched analysis was not performed, as it would have further reduced the effective sample size without being expected to modify the neutral association between the two DAT regimens and clinical outcomes. Third, no information was available regarding the PCI complexity nor the doses of DOAC use which both may impact on the overall efficacy and safety of any DAT regimen. Finally, although statistically not significant, clopidogrel might have a numerical advantage since more patients had been involved in the clopidogrel-based DAT group. Thus, the generalizability of our results should be interpreted with caution and further validated through dedicated randomized controlled trials.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eIn the population of consecutive patients on OAC for various indications undergoing PCI who were enrolled in the Italian, multi-center, prospective PERSEO registry, no significant difference in the occurrence of NACE was observed between clopidogrel-based vs. aspirin-based DAT following an initial course of TAT. While established predictors of adverse events following PCI, such as advanced age, CKD, anemia, CHA\u003csub\u003e2\u003c/sub\u003eD\u003csub\u003eS\u003c/sub\u003e-VASc and HAS-BLED scores, and number of stents implanted, were confirmed also in this OAC population, no clinical or procedural variables were identified to guide the selection of clopidogrel vs. aspirin in DAT combination. Besides the demonstration of phenotypic or genotypic non-responsiveness to clopidogrel, or the need for concomitant administration of PPI, which regardless of the agent has been recently shown to decrease the efficacy of clopidogrel monotherapy following PCI (32), the choice between clopidogrel-based vs. aspirin based DAT should be left at present at the discretion of the attending physician.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFUNDING\u003c/h2\u003e \u003cp\u003eThis work was not supported by any sponsor or funder.\u003c/p\u003e \u003cp\u003eDATA AVAILABILITY\u003c/p\u003e \u003cp\u003eAnonymized raw data is available from authors upon reasonable request.\u003c/p\u003e \u003cp\u003eDECLARATION CONFLICTS OF INTEREST.\u003c/p\u003e \u003cp\u003eA.R. declares Lecture fees from and/or consulting for Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer BMS outside the submitted work. G.A. declares personal fees and non-financial support from Daiichi Sankyo, Amgen, and Boehringer Ingelheim, and personal fees from AstraZeneca, Chiesi, and Sanofi, outside the submitted work. A.S. declares consulting for Novo Nordisk, and Daiichi Sankyo outside the submitted work. The other authors declare no conflict of interest.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization, A.R.; methodology, A.R., G.P. , and A.S.; validation, A.R., and A.S; formal analysis, G.P.; data curation, S.D.R., P.C., C.M., B.C., M.C., V.P., G.A., and A.S.; writing, original draft preparation, A.R, G.A., and G.P.; writing, review and editing, A.R., G.P., and A.S. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDewilde WJ, Oirbans T, Verheugt FW, Kelder JC, De Smet BJ, Herrman JP, Adriaenssens T, Vrolix M, Heestermans AA, Vis MM, Tijsen JG, van 't Hof AW, ten Berg JM, WOEST study investigators (2013) Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 381:1107\u0026ndash;1115. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(12)62177-1\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(12)62177-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, Birmingham M, Ianus J, Burton P, van Eickels M, Korjian S, Daaboul Y, Lip GY, Cohen M, Husted S, Peterson ED, Fox KA (2016) Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med 375:2423\u0026ndash;2434. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa1611594\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa1611594\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, Maeng M, Merkely B, Zeymer U, Gropper S, Nordaby M, Kleine E, Harper R, Manassie J, Januzzi JL, Ten Berg JM, Steg PG, Hohnloser SH, RE-DUAL PCI Steering Committee and Investigators (2017) Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med 377:1513\u0026ndash;1524. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa1708454\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa1708454\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLopes RD, Heizer G, Aronson R, Vora AN, Massaro T, Mehran R, Goodman SG, Windecker S, Darius H, Li J, Averkov O, Bahit MC, Berwanger O, Budaj A, Hijazi Z, Parkhomenko A, Sinnaeve P, Storey RF, Thiele H, Vinereanu D, Granger CB, Alexander JH, AUGUSTUS Investigators (2019) Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. N Engl J Med 380:1509\u0026ndash;1524. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa1817083\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa1817083\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003eEpub 2019 Mar 17. PMID: 30883055\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVranckx P, Valgimigli M, Eckardt L, Tijssen J, Lewalter T, Gargiulo G, Batushkin V, Campo G, Lysak Z, Vakaliuk I, Milewski K, Laeis P, Reimitz PE, Smolnik R, Zierhut W, Goette A (2019) Edoxaban-based versus vitamin K antagonist-based antithrombotic regimen after successful coronary stenting in patients with atrial fibrillation (ENTRUST-AF PCI): a randomised, open-label, phase 3b trial. Lancet 394(10206):1335\u0026ndash;1343. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(19)31872-0\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(19)31872-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumbhani DJ, Cannon CP, Beavers CJ, Bhatt DL, Cuker A, Gluckman TJ, Marine JE, Mehran R, Messe SR, Patel NS, Peterson BE, Rosenfield K, Spinler SA, Thourani VH (2021) 2020 ACC Expert Consensus Decision Pathway for Anticoagulant and Antiplatelet Therapy in Patients With Atrial Fibrillation or Venous Thromboembolism Undergoing Percutaneous Coronary Intervention or With Atherosclerotic Cardiovascular Disease: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 77:629\u0026ndash;658. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jacc.2020.09.011\u003c/span\u003e\u003cspan address=\"10.1016/j.jacc.2020.09.011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Gelder IC, Rienstra M, Bunting KV, Casado-Arroyo R, Caso V, Crijns HJGM, De Potter TJR, Dwight J, Guasti L, Hanke T, Jaarsma T, Lettino M, L\u0026oslash;chen ML, Lumbers RT, Maesen B, M\u0026oslash;lgaard I, Rosano GMC, Sanders P, Schnabel RB, Suwalski P, Svennberg E, Tamargo J, Tica O, Traykov V, Tzeis S, Kotecha D, ESC Scientific Document Group (2024) 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 45:3314\u0026ndash;3414. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/eurheartj/ehae176\u003c/span\u003e\u003cspan address=\"10.1093/eurheartj/ehae176\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePraz F, Borger MA, Lanz J, Marin-Cuartas M, Abreu A, Adamo M, Ajmone Marsan N, Barili F, Bonaros N, Cosyns B, De Paulis R, Gamra H, Jahangiri M, Jeppsson A, Klautz RJM, Mores B, P\u0026eacute;rez-David E, P\u0026ouml;ss J, Prendergast BD, Rocca B, Rossello X, Suzuki M, Thiele H, Tribouilloy CM, Wojakowski W, ESC/EACTS Scientific Document Group (2025) 2025 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 46:4635\u0026ndash;4736. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/eurheartj/ehaf194\u003c/span\u003e\u003cspan address=\"10.1093/eurheartj/ehaf194\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSofi F, Marcucci R, Gori AM, Giusti B, Abbate R, Gensini GF (2010) Clopidogrel non-responsiveness and risk of cardiovascular morbidity. updated meta-analysis Thromb Haemost 103:841\u0026ndash;848. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1160/TH09-06-0418\u003c/span\u003e\u003cspan address=\"10.1160/TH09-06-0418\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLau WC, Waskell LA, Watkins PB, Neer CJ, Horowitz K, Hopp AS, Tait AR, Carville DG, Guyer KE, Bates ER (2003) Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation 107:32\u0026ndash;37. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/01.cir.0000047060.60595.cc\u003c/span\u003e\u003cspan address=\"10.1161/01.cir.0000047060.60595.cc\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartini L, Lisi M, Pompei G, Arioti M, Bendandi F, Henein MY, Cameli M, Rubboli A (2025) Antiplatelet Therapy in Atrial Fibrillation Patients on Direct Oral Anticoagulants Undergoing Percutaneous Coronary Intervention: Which and How. J Clin Med 14:6331. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/jcm14176331\u003c/span\u003e\u003cspan address=\"10.3390/jcm14176331\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim HK, Tantry US, Smith SC Jr, Jeong MH, Park SJ, Kim MH, Lim DS, Shin ES, Park DW, Huo Y, Chen SL, Bo Z, Goto S, Kimura T, Yasuda S, Chen WJ, Chan M, Aradi D, Geisler T, Gorog DA, Sibbing D, Lip GYH, Angiolillo DJ, Gurbel PA, Jeong YH (2021) The East Asian Paradox: An Updated Position Statement on the Challenges to the Current Antithrombotic Strategy in Patients with Cardiovascular Disease. Thromb Haemost 121:422\u0026ndash;432. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1055/s-0040-1718729\u003c/span\u003e\u003cspan address=\"10.1055/s-0040-1718729\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim S, Park S, Kim H, Aung N, Kim SH, Chang K, Choi Y (2025) Clinical outcomes with the use of aspirin vs. clopidogrel as a combination therapy with direct oral anticoagulant after coronary stent implantation in patients with atrial fibrillation. Eur Heart J Cardiovasc Pharmacother 11:532\u0026ndash;539. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/ehjcvp/pvaf043\u003c/span\u003e\u003cspan address=\"10.1093/ehjcvp/pvaf043\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNatsuaki M, Watanabe H, Morimoto T, Yamamoto K, Obayashi Y, Nishikawa R, Kimura T, Ando K, Suwa S, Isawa T, Takenaka H, Ishikawa T, Tamura T, Kawahatsu K, Hayashi F, Akao M, Serikawa T, Mori H, Kawamura T, Hagikura A, Shibata N, Ono K, Kimura T (2025) Aspirin Versus Clopidogrel Beyond 1 Month After PCI in Patients With Oral Anticoagulation. Circ Cardiovasc Interv 18:e015495. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/CIRCINTERVENTIONS.125.015495\u003c/span\u003e\u003cspan address=\"10.1161/CIRCINTERVENTIONS.125.015495\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSciahbasi A, Gargiulo G, Talarico GP, Cesaro A, Zilio F, De Rosa S, Talanas G, Tebaldi M, And\u0026ograve; G, Rigattieri S, Misuraca L, Cortese B, Imperadore F, Lucci V, Guiducci V, Renda G, Zezza L, Versaci F, Giannico MB, Caruso M, Spaccarotella C, Calabr\u0026ograve; P, Esposito G, Tarantini G, Musumeci G, Rubboli A (2022) Design of the PERSEO Registry on the management of patients treated with oral anticoagulants and coronary stent. J Cardiovasc Med (Hagerstown) 23:738\u0026ndash;743. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2459/JCM.0000000000001372\u003c/span\u003e\u003cspan address=\"10.2459/JCM.0000000000001372\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW, Academic Research Consortium (2007) Clinical end points in coronary stent trials: a case for standardized definitions.Circulation 115(17):2344-51. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/CIRCULATIONAHA.106.685313\u003c/span\u003e\u003cspan address=\"10.1161/CIRCULATIONAHA.106.685313\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H (2011) Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 123:2736\u0026ndash;2747. 10.1161 CIRCULATIONAHA.110.009449\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSciahbasi A, De Rosa S, Gargiulo G, Giacoppo D, Calabr\u0026ograve; P, Talarico GP, Zilio F, Talanas G, Tebaldi M, And\u0026ograve; G, Rigattieri S, Misuraca L, Cortese B, Musuraca G, Lucci V, Guiducci V, Renda G, Zezza L, Versaci F, Giannico MB, Caruso M, Fischetti D, Colletta M, Santarelli A, Larosa C, Iannone A, Esposito G, Tarantini G, Musumeci G, Rubboli A (2024) Management of Patients Treated With Oral Anticoagulant Therapy Undergoing Percutaneous Coronary Intervention With Stent Implantation: The PERSEO Registry. J Cardiovasc Pharmacol 84:457\u0026ndash;467. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/FJC.0000000000001607\u003c/span\u003e\u003cspan address=\"10.1097/FJC.0000000000001607\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoo BK, Kang J, Park KW, Rhee TM, Yang HM, Won KB, Rha SW, Bae JW, Lee NH, Hur SH, Yoon J, Park TH, Kim BS, Lim SW, Cho YH, Jeon DW, Kim SH, Han JK, Shin ES, Kim HS, HOST-EXAM investigators (2021) Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention (HOST-EXAM): an investigator-initiated, prospective, randomised, open-label, multicentre trial. Lancet 397:2487\u0026ndash;2496. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(21)01063-1\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(21)01063-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoi KH, Park YH, Lee JY, Jeong JO, Kim CJ, Yun KH, Lee HC, Chang K, Park MW, Bae JW, Doh JH, Cho BR, Kim HY, Kim W, Kim U, Rha SW, Hong YJ, Lee HJ, Ahn SG, Kim DI, Cho JH, Her SH, Jeon DS, Han SH, Lee JB, Lee CW, Kang D, Lee JM, Park TK, Yang JH, Lee SY, Choi SH, Gwon HC, Song YB, Hahn JY, SMART-CHOICE 3 investigators (2025) Efficacy and safety of clopidogrel versus aspirin monotherapy in patients at high risk of subsequent cardiovascular event after percutaneous coronary intervention (SMART-CHOICE 3): a randomised, open-label, multicentre trial. Lancet 405:1252\u0026ndash;1263. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(25)00449-0\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(25)00449-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWani SA, Naveed MA, Azeem B, Ashraf S, Ali A, Ali T, Fatima F, Shah M, Neppala S, Ahmed R (2025) Comparative outcomes of clopidogrel vs aspirin monotherapy in post-PCI patients: An updated systematic review and meta-analysis. Cardiovasc Revasc Med 80:122\u0026ndash;130. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.carrev.2025.06.006\u003c/span\u003e\u003cspan address=\"10.1016/j.carrev.2025.06.006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S, ESC Scientific Document Group (2024). 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. ;45(36):3415\u0026ndash;3537. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/eurheartj/ehae177\u003c/span\u003e\u003cspan address=\"10.1093/eurheartj/ehae177\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 39210710\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValgimigli M, Choi KH, Giacoppo D, Gragnano F, Kimura T, Watanabe H, Kim HS, Kang J, Park KW, Pettersen A\u0026Aring;, Woodward M, Bhatt DL, Calabr\u0026ograve; P, Angiolillo DJ, Mehran R, Song YB, Hahn JY (2025) Clopidogrel versus aspirin for secondary prevention of coronary artery disease: a systematic review and individual patient data meta-analysis. Lancet 406:1091\u0026ndash;1102. 10.1016S0140-6736(25)01562-4\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDorsam RT, Kunapuli SP (2004) Central role of the P2Y12 receptor in platelet activation. J Clin Invest 113:340\u0026ndash;345. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1172/JCI20986\u003c/span\u003e\u003cspan address=\"10.1172/JCI20986\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee PC, Kini AS, Ahsan C, Fisher E, Sharma SK (2004) Anemia is an independent predictor of mortality after percutaneous coronary intervention. J Am Coll Cardiol 44(3):541\u0026ndash;546. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jacc.2004.04.047\u003c/span\u003e\u003cspan address=\"10.1016/j.jacc.2004.04.047\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeng W, Wang D, Wan Y, Lai S, Ding Y, Wang X (2024) Prediction models for major adverse cardiovascular events after percutaneous coronary intervention: a systematic review. Front Cardiovasc Med 10:1287434. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fcvm.2023.1287434\u003c/span\u003e\u003cspan address=\"10.3389/fcvm.2023.1287434\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePuurunen MK, Kiviniemi T, Schlitt A, Rubboli A, Dietrich B, Karjalainen P, Nyman K, Niemel\u0026auml; M, Lip GY, Airaksinen KE (2014) CHADS2, CHA2DS2-VASc and HAS-BLED as predictors of outcome in patients with atrial fibrillation undergoing percutaneous coronary intervention. Thromb Res 133:560\u0026ndash;566. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.thromres.2014.01.007\u003c/span\u003e\u003cspan address=\"10.1016/j.thromres.2014.01.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePuurunen M, Kiviniemi T, Nammas W, Schlitt A, Rubboli A, Nyman K, Karjalainen P, Kirchhof P, Lip GY, Airaksinen JK (2014) Impact of anaemia on clinical outcome in patients with atrial fibrillation undergoing percutaneous coronary intervention: insights from the AFCAS registry. BMJ Open 4:e004700. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmjopen-2013-004700\u003c/span\u003e\u003cspan address=\"10.1136/bmjopen-2013-004700\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLahtela HM, Kiviniemi TO, Puurunen MK, Schlitt A, Rubboli A, Ylitalo A, Valencia J, Lip GY, Airaksinen KE (2015) Renal Impairment and Prognosis of Patients with Atrial Fibrillation Undergoing Coronary Intervention - The AFCAS Trial. PLoS ONE 10:e0128492. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0128492\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0128492\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLahtela HM, Bah A, Kiviniemi T, Nammas W, Schlitt A, Rubboli A, Karjalainen PP, Proietti M, Hartikainen JEK, Lip GYH, Airaksinen KEJ (2017) Outcome of octogenarians with atrial fibrillation undergoing percutaneous coronary intervention: insights from the AFCAS registry. Clin Cardiol 40:1264\u0026ndash;1270. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/clc.22821\u003c/span\u003e\u003cspan address=\"10.1002/clc.22821\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRuff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM (2014) Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 383(9921):955\u0026ndash;962. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(13)62343-0\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(13)62343-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNishikura T, Yamamoto K, Wakabayashi K, Natsuaki M, Watanabe H, Morimoto T, Obayashi Y, Nishikawa R, Kimura T, Ando K, Suwa S, Isawa T, Takenaka H, Ishikawa T, Onishi Y, Hibi K, Kawai K, Murakami T, Takasaki A, Higashitani N, Nakano M, Ono K, Kimura T, STOPDAPT-3 investigators (2025) Effect of Proton Pump Inhibitors in Patients Undergoing Percutaneous Coronary Intervention With Aspirin-Free Strategy. JACC Asia Nov 13:S2772-3747(25)00542-3. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jacasi.2025.09.015\u003c/span\u003e\u003cspan address=\"10.1016/j.jacasi.2025.09.015\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"620\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 620px;\"\u003e\n \u003cp\u003eTable 1. Baseline characteristics.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClopidogrel-based\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eDAT (N=769\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAspirin-based DAT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN=220\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eAge, median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e76 [70,81]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e74 [68,81]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eMale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e556 (72.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e166 (75.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.353\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eBMI, median IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e26.5 [24.3, 29.4]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e26.9 [24.5, 29.3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.956\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eDiabetes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e271 (35.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e76 (34.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.849\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eHypertension, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e672 (87.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e188 (85.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.453\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eSmoking habits, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e279 (36.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e89 (40.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.259\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eeGFR (ml/min 1.73 m\u003csup\u003e2\u003c/sup\u003e), median\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e68.9 [52.4, 86.7]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e70.1 [54.5, 86.5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.523\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eLVEF, median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e50 [38, 55]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e48 [38, 55]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.824\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eCHA\u003csub\u003e2\u003c/sub\u003eDS\u003csub\u003e2\u003c/sub\u003eVASc score, median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e4 [3, 5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e4 [3, 5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eHAS-BLED score,\u0026nbsp;median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e4 [3, 4]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e3 [3, 4]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.061\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eCHARLSON score,\u0026nbsp;median [IQR]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e2 [1, 3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e2 [1, 4]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.350\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eDOAC use, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e664 (86.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e181 (82.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.120\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003ePPI use, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e721 (93.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e203 (92.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.433\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 620px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eM\u003c/strong\u003e\u003cstrong\u003eedical history\u003c/strong\u003e\u003cstrong\u003e, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003ePrevious MI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e176 (22.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e59 (26.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.227\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003ePrevious PCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e190 (24.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e67 (30.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003ePrevious CABG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e59 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e22 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.267\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003ePrevious bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e48 (6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e11 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.493\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003ePrevious stroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e1 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e2 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003ePrevious TIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e92 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e20 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.236\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003ePAD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e168 (21.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e59 (26.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.122\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eCKD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e274 (35.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e73 (33.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.502\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eHF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e240 (31.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e79 (35.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.189\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eCOPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e108 (14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e33 (15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.721\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eLiver disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e23 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e9 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.441\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eAlcohol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e6 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e3 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.422\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eAnaemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e83 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e17 (7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.183\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003ePeptic ulcer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e15 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e2 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.295\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eCancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e57 (7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e13 (5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.443\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 620px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical presentation, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eACS\u003c/p\u003e\n \u003cp\u003eHF\u003c/p\u003e\n \u003cp\u003eArrhythmia\u003c/p\u003e\n \u003cp\u003eCCS\u003c/p\u003e\n \u003cp\u003eSyncope\u003c/p\u003e\n \u003cp\u003eHeart valve disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e477 (62)\u003c/p\u003e\n \u003cp\u003e113 (14.7)\u003c/p\u003e\n \u003cp\u003e26 (3.4)\u003c/p\u003e\n \u003cp\u003e138 (17.9)\u003c/p\u003e\n \u003cp\u003e4 (0.5)\u003c/p\u003e\n \u003cp\u003e3 (0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e134 (60.9)\u003c/p\u003e\n \u003cp\u003e31 (14.1)\u003c/p\u003e\n \u003cp\u003e12 (5.5)\u003c/p\u003e\n \u003cp\u003e42 (19.1)\u003c/p\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003cp\u003e1 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.474\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 620px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndication for OAC\u003c/strong\u003e\u003cstrong\u003e, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eAF\u003c/p\u003e\n \u003cp\u003eVTE\u003c/p\u003e\n \u003cp\u003eMechanical\u0026nbsp;heart valve\u003c/p\u003e\n \u003cp\u003eLV thrombus\u003c/p\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e686 (89.2)\u003c/p\u003e\n \u003cp\u003e34 (4.4)\u003c/p\u003e\n \u003cp\u003e16 (2.1)\u003c/p\u003e\n \u003cp\u003e19 (2.5)\u003c/p\u003e\n \u003cp\u003e14 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e193 (87.7)\u003c/p\u003e\n \u003cp\u003e11 (5)\u003c/p\u003e\n \u003cp\u003e6 (2.7)\u003c/p\u003e\n \u003cp\u003e8 (3.6)\u003c/p\u003e\n \u003cp\u003e2 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.471\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 620px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eProcedural characteristics\u003c/strong\u003e\u003cstrong\u003e, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eRadial access\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e678 (88.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e205 (93.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 199px;\"\u003e\n \u003cp\u003eN. of implanted stents\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e\u0026gt;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e442 (57.5)\u003c/p\u003e\n \u003cp\u003e209 (27.2)\u003c/p\u003e\n \u003cp\u003e72 (9.4)\u003c/p\u003e\n \u003cp\u003e46 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 163px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e125 (56.8)\u003c/p\u003e\n \u003cp\u003e65 (29.6)\u003c/p\u003e\n \u003cp\u003e21 (9.6)\u003c/p\u003e\n \u003cp\u003e9 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e0.662\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 620px;\"\u003e\n \u003cp\u003eACS: acute coronary syndrome; DAT: double antithrombotic therapy; IQR: interquartile range; BMI: body mass index; MI: myocardial infarction; PCI: percutaneous coronary intervention; CABG: coronary artery bypass grafting; TIA: transient ischaemic attack; PAD: peripheral artery disease; CKD: chronic kidney disease; eGFR: estimated glomerular filtration rate; HF: heart failure; CCS: chronic coronary syndrome; LV: left ventricular; LVEF: left ventricular ejection fraction; COPD: chronic obstructive pulmonary disease; OAC: oral anticoagulant; AF: atrial fibrillation; PE: pulmonary embolism; VTE: venous thromboembolism; DOAC: direct oral anticoagulant; PPI: proton-pump inhibitor. \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"620\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 620px;\"\u003e\n \u003cp\u003eTable 2. Clinical outcomes.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdverse clinical events\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClopidogrel\u003c/strong\u003e\u003cstrong\u003e-based DAT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN=769\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAspirin-based DAT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN=220\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary endpoint\u003c/strong\u003e\u003cstrong\u003e, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eNACE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e147 (19.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e44 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.770\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSecondary endpoints, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eMACCE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e79 (10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e19 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.474\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eAll-cause death\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e66 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e20 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.813\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eCardiac death\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e14 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e8 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.107\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eStroke/TIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e9 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e2 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.745\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eNon-fatal MI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e17 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e2 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.215\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eStent thrombosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e6 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e1 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.611\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eTVR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e11 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e1 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.244\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eMajor bleedings (BARC 3-5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e17 (2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e3 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.431\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 196px;\"\u003e\n \u003cp\u003eClinically relevant bleedings (BARC 2, 3, 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e57 (7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 171px;\"\u003e\n \u003cp\u003e16 (7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e0.944\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 620px;\"\u003e\n \u003cp\u003eDAT: double antithrombotic therapy; NACE: net adverse clinical events; MACCE: major adverse cardiac/cerebral events; TIA: transient ischemic attack; MI: myocardial infarction; TVR: target vessel revascularization.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"642\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 642px;\"\u003e\n \u003cp\u003eTable 3. Cox regression analysis for NACE at median follow-up time (12.3 months) including both univariable and multivariable analysis.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR multivariable analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eClopidogrel- vs. aspirin-based DAT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e1.06 (0.75, 1.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.756\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e1.04 (1.02, 1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.02 (1.00, 1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.027\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e0.89 (0.65,1.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.463\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e0.97 (0.93, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.062\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003ePrevious MI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e0.95 (0.68, 1.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.770\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003ePrevious bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e1.57 (0.94, 2.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.086\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003ePrevious stroke/TIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e0.67 (0.40, 1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eCKD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e1.82 (1.37, 2.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.49 (1.08, 2.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eAnaemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e2 (1.37, 2.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.62 (1.10, 2.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eCancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e1.58 (0.98, 2.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eCHA2DS2-VASc\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e1.21 (1.10, 1.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.12 (0.99, 1.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.080\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eHAS-BLED\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e1.23 (1.08, 1.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.92 (0.77, 1.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.376\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eRadial access\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e0.67 (0.45, 1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eN. of implanted stents\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e1.18 (1.04, 1.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.22 (1.07, 1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eDAT \u0026gt; 6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e1.03 (0.71, 1.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.888\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003eDOAC vs. VKA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e0.67 (0.47, 0.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 87px;\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.69 (0.48, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp\u003e0.047\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 642px;\"\u003e\n \u003cp\u003eNACE: net adverse clinical events; HR: hazard ratio; CI: confidence interval; DAT:double antithrombotic therapy; BMI: body mass index; MI: myocardial infarction; TIA: transient ischemic attack; CKD: chronic kidney disease; DOAC: direct oral anticoagulant; VKA: vitamin K-antagonist.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"619\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 619px;\"\u003e\n \u003cp\u003eTable 4. Univariable and multivariable analysis for clinical adverse events according to clopidogrel-based vs. aspirin-based DAT.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eEndpoint\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eHR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eHR multivariable (adjusted for age, CKD, anaemia, number of stents, type of OAC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003ep-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eNACE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e1.06 (0.75, 1.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.756\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.98 (0.70, 1.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.923\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eMACCE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e1.42 (0.86, 2.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.172\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.27 (0.76, 2.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.359\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eAll-cause death\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e1.14 (0.69, 1.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.608\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.99 (0.60, 1.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.984\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eCardiac death\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.56 (0.23, 1.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.190\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.46 (0.19, 1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.090\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eStroke/TIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e1.37 (0.29, 6.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.690\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.28 (0.27, 5.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.753\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eNon-fatal MI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e2.59 (0.60, 11.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.204\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e2.26 (0.52, 9.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.279\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eBARC 2-5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e1.13 (0.65, 1.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.679\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.03 (0.59, 1.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.913\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003eBARC 3-5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e1.85 (0.54, 6.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e0.326\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.60 (0.46, 5.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e0.910\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 619px;\"\u003e\n \u003cp\u003eDAT: double antithrombotic therapy; HR: hazard ratio; CI: confidence interval; CKD: chronic kidney disease; NACE: net adverse clinical events; MACCE: major adverse cardiac/cerebral events; CV: cardiovascular; TIA: transient ischemic attack; MI: myocardial infarction;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Oral anticoagulation, percutaneous coronary intervention, coronary artery disease, clopidogrel, aspirin","lastPublishedDoi":"10.21203/rs.3.rs-8574706/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8574706/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIn patients on oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI), clopidogrel is currently the preferred antiplatelet agent to be given in double antithrombotic therapy (DAT). To explore whether aspirin could be an alternative option, a post-hoc analysis of the Italian, multi-center, prospective PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) registry was performed. Out of the 989 patients included in the analysis, 769 (78%) received clopidogrel and 220 (22%) aspirin. Baseline characteristics were largely comparable between the two groups, particularly as regards the indications for PCI and OAC, with acute coronary syndrome and atrial fibrillation respectively, being the most common, the number of stents implanted, and the use of direct oral anticoagulants and proton-pump inhibitors. At a median follow-up of 12.3 months, the primary outcome of net adverse cardiac events (NACE), including major adverse cardiac/cerebral events (MACCE) and major bleeding was similar with clopidogrel-based and aspirin-based DAT (19.1% vs. 20.0%; p\u0026thinsp;=\u0026thinsp;0.770). Secondary outcomes of MACCE, all-cause death, cardiac death, non-fatal myocardial infarction, stent thrombosis, non-fatal stroke/transient ischemic attack, target vessel revascularization, and major and clinically relevant bleeding were also comparable. Multivariable analyses confirmed no association between type of DAT and outcomes. Survival analyses showed overlapping event rates between clopidogrel-based and aspirin-baed DAT. In patients on OAC undergoing PCI, no significant difference in the occurrence of NACE was observed between clopidogrel-based and aspirin-based DAT. While waiting for further data, individualized physician\u0026rsquo;s choice of the DAT regimen appears indicated.\u003c/p\u003e","manuscriptTitle":"Clopidogrel-Based vs. Aspirin-Based Double Antithrombotic Therapy Following Percutaneous Coronary Intervention with Stent in Patients on Oral Anticoagulation. A Post-Hoc Analysis of the Perseo Registry","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-16 09:15:29","doi":"10.21203/rs.3.rs-8574706/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9641305e-1f0a-4b93-b572-56dbd897fa0e","owner":[],"postedDate":"January 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-27T16:01:19+00:00","versionOfRecord":{"articleIdentity":"rs-8574706","link":"https://doi.org/10.1007/s11239-026-03286-4","journal":{"identity":"journal-of-thrombosis-and-thrombolysis","isVorOnly":false,"title":"Journal of Thrombosis and Thrombolysis"},"publishedOn":"2026-04-20 15:57:53","publishedOnDateReadable":"April 20th, 2026"},"versionCreatedAt":"2026-01-16 09:15:29","video":"","vorDoi":"10.1007/s11239-026-03286-4","vorDoiUrl":"https://doi.org/10.1007/s11239-026-03286-4","workflowStages":[]},"version":"v1","identity":"rs-8574706","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8574706","identity":"rs-8574706","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}