Study on Optimizing Antiplatelet Therapy for Patients Undergoing Coronary Artery Stenting Complicated with High On-treatment Platelet Reactivity

Objective: The Purpose of this study was to evaluate the feasibility, efficacy andsafety of optimizing antiplatelet therapy for patients with acute coronary syndrome(ACS) complicated high on-treatment platelet reactivity (HPR) after coronary stentingin real world practice.Methods: This study was a prospective, randomized, open-label multicentre study.From March2009to February2011, a total of840ACS patients were enrolled from theGeneral Hospital of Shenyang Military Region,463Hospital of PLA and the FirstHospital of China Medical University. Inclusion criteria were:(1) Admitted for ACSand received at least one drug-eluting stents implantation in the index procedure.(2)HPR under regular clopidogrel treatment, which was defined as a20μmol/L adenosinediphosphate (ADP) induced platelet aggregation (PA)rate≥55%by light transmittanceaggregometry (LTA) at24hours after clopidogrel loading (300mg). The eligiblepatients were randomly divided into two groups by the ratio of1:2. Patients in thestandard group (n=280) received standard dual antiplatelet therapy, aspirin300mg/dfor30days followed with100mg/d indefinitely and clopidogrel75mg/d for one year.Patients in the intensive group (n=560) received clopidogrel150mg/d for3days, thena PA test was performed and the antiplatelet treatment was changed accordingly:patients with attenuated HPR (PA<55%) remain the double dose clopidogrel treatment;patients with PA still higher than55%were1:1randomly assigned to receive cilostazol50mg twice a day on the top of clopidogrel150mg/d or cilostazol100mg twice a dayon the top of clopidogrel75mg/d. Patients in the intensive group received the sameaspirin regimen for standard group after30days, clopidogrel maintenance dose wasswitched to75mg/d for all patients and lasted for1year. Cilostazol treatment was lasted for6months with unchanged dose according to study protocol. All patientsreceived a PA test at30days after randomization. The primary end point was majorischemic events at1year, defined as a composite of cardiac death, nonfatal myocardialinfarction and stroke. Secondary end points included ischemic driven target vesselsrevascularization, stent thrombosis, recurrent angina pectoris, non-target vesselrevascularization. Safety end points were TIMI major, minor and minimal bleedingevents.Results: Between the two groups, age, sex, weight index, the proportion of highblood pressure, smoking, stroke, prior myocardial infarction and the stent length anddiameter were not significantly different (P>0.05). At30days, attenuation of HPR wasmore frequently in the intensive group compared with the standard group（69.9%vs55.7%，P<0.001）.Patients received different dose of cilostazol had similar rate of HPRattenuation（cilostazol50mg:68.8%vs cilostzaol100mg:68.2%；P=0.98）.The rate ofprimary events at one-year follow-up were similar between the two groups (0.54%vs.1.80%, p=0.13) The rate of cardiac death (0vs.0.72%), nonfatal myocardialinfarction (0.36%vs.0.36%) and ischemic stroke (0.18%vs.0.72%) were notsignificantly different between the two groups (P>0.05). Patients in the intensive grouphad lower rates of ischemia driven target-vessel revascularization (2.14%vs.5.3%, P=0.021) and recurrent angina (8.75%vs.18.6%, P=0.001) compared with those ofstandard group. while the incidence of the primary, the minor and the minimal bleedingevents were not increased in the intensive group compared with the standard groupmajor（0.36%vs.0.72%,p=0.41）, minor（0vs.1.07%, p=0.037） and minimalbleeding (6.96%vs.4.29%，P=0.17).Conclusions: Intensive antiplatelet therapy with high maintenance clopidogeland/or additional cilostazol is effective in attenuating HPR, decreasing incidences ofischemia driven target vessel revascularization and recurrent angina, not at a price ofexcessive risk of bleeding, in patients with ACS undergoing coronary stenting. However,the clinical benefits of reducing the risk of major ischemic events (cardiac death,myocardial infarction, stroke) were not observed in the present study.