Indobufen Versus Aspirin Combined With Clopidogrel Used For Dual Antiplatelet Therapy After Drug-eluting Stent Implantation: Randomized Controlled Study

Objective Indobufen,as a new antiplatelet drug,has been considered for antiplatelet replacement therapy before thrombolysis in patients with ST-segment elevation myocardial infarction who are intolerant of aspirin in the gastrointestinal tract.The aim of this trial was to investigate the efficacy and safety of antiplatelet therapy with indobufen in patients with troponin negative coronary artery stent implantation within one year compared with aspirin.Methods This trial is a prospective,open,non-inferiority,1:1 randomized controlled exploratory study.We selected some patients with coronary artery disease(CAD)who underwent percutaneous coronary intervention(PCI)from June 2018 to February 2019 in the Department of Cardiovascular Medicine of our hospital.60 patients who met the inclusion and exclusion criteria were selected and randomly assigned to the experimental group and the control group with 30 patients each.Within 24 hours after stent implantation,the experimental group received indobufen(100mg bid)plus clopidogrel(75mg qd),and the control group received aspirin(100mg qd)plus clopidogrel(75mg qd)dual antiplatelet therapy regularly for 12 months,at the same time,segmental follow-up was performed on the 1st day,the 1st month,the 3rd month,the 6th month and the 12 th month after stent implantation.The primary end point of net adverse clinical and cerebral events(NACCE)was composite endpoints which composited of death from any cause,non-fatal myocardial infarction,ischemic stroke,stent thrombosis(possibly or definitively)and type 2,3 or 5 hemorrhage defined by Bleeding academic research consortium(BARC).The secondary endpoints included: 1)Major adverse cardiovascular events(MACE)including cardiac death,non-fatal myocardial infarction,or stent thrombosis(possibly or definitively)as efficacy endpoints;2)All-types BARC bleeding as safety endpoints;3)Adverse events of upper gastrointestinal tract.Other endpoints included: NACCE at each study visit time point,discontinuation or replacement of medication.The demographic characteristics and baseline conditions of the two groups were described and compared,and the differences of the endpoints were analyzed.The relationship between the time and event rate of the main end point and its components was analyzed by Kaplan-Meier method,and the difference was compared by log-rank test.The Hazard ratio(HR)was calculated by Cox proportional regression analysis.In addition,the association between the two groups of treatment plans and the clinical end point events within 12 months was analyzed under different Precise-DAPT scores and Syntax scores.P<0.05(2-sided)was considered significant unless other-wise specified.Results(1)There was no significant difference in the incidence of every end point events between the experimental group(indobufen combined with clopidogrel)and the control group(aspirin combined with clopidogrel)during the 12 months follow-up period.(2)The primary endpoint was analyzed by Kaplan-Meier method.The incidence of NACCE was 6.7% in the experimental group and 16.7% in the control group(HR,0.238 [95% CI,0.041-1.375];Logrank P=0.16).The choice of two dual antiplatelet regimens was not statistically associated with the occurrence of NACCE.(3)The incidence of major bleeding(BARC type 2,3 and 5)at 12 months was 3.33% and 13.33%(HR,0.238 [95% CI,0.041-1.375];Log-rank P=0.16)in the experimental group and the control group,and there was no statistical correlation between the two treatment regimens and the occurrence of major bleeding.(4)There was no significant difference in the incidence of upper gastrointestinal adverse events and any bleeding events between the experimental group and the control group;(5)There was no statistical correlation between the incidence of clinical endpoint events within 12 months and the choice of two treatment regimens in patients with each risk of Syntax score.(6)There was no statistical correlation between the incidence of any bleeding event within 12 months and the choice of the two treatment options in patients with each risk levels of the Precise-DAPT score.Conclusions Indobufen combined with clopidogrel dual antiplatelet therapy did not significantly reduce the incidence of death,non-fatal myocardial infarction,ischemic stroke and major bleeding in troponin-negative-patients with CAD who received percutaneous coronary intervention and implanted at least one drug-eluting stent,but could play a stable antiplatelet role without increasing stent thrombosis Risk and occurrence of upper gastrointestinal adverse events.