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 and safetyof optimizing antiplatelet therapy for patients with acute coronary syndrome (ACS)complicated high on-treatment platelet reactivity (HPR) after coronary stenting in realworld practice.Methods:This study was a prospective, open-label, randomizedstudy. From March2009to February2011, a total of300inpatient ACS patients were enrolled from theGeneral Hospital of Shenyang Military Region. Inclusion criteria were:(1) Admitted forACS and received at least one drug-eluting stents (DES) implantation in the indexprocedure.(2) HPR under regular clopidogrel treatment, which was defined asa20μmol/L adenosine diphosphate induced platelet aggregation rate≥55%by lighttransmittance aggregometry at24hrs after clopidogrel loading (300mg24). Theeligible patients were randomly divided into two groups by the ratio of2:1(.1)Patientsin the standard group (n=100) received standard dual antiplatelet therapy, i.e. aspirin300mg/d for30days followed with100mg/d indefinitely and clopidogrel75mg/d forone year.(2) Patients in the intensive group (n=200) received clopidogrel150mg/dfor3days, then a PA test was performed and the antiplatelet treatment was changedaccordingly: patient with attenuated HPR (PA<55%) remain the double doseclopidogrel treatment(n=104); 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 day on the top of clopidogrel75mg/d.Patients in theintensive group received the same aspirin regimen for standard group After30days,clopidogrel maintenance dose was switched to75mg/d for all patients and lasted for1year. Cilostazol treatment was lasted for6months with unchanged dose according to study protocol. All patients received a PA test at30days after randomization. Theefficacy end point was major ischemic events at2year, defined as a composite of cardiacdeath, nonfatal myocardial infarction and stroke. Secondary end points includedischemic driven target vessels revascularization, stent thrombosis, recurrent anginapectoris, non-target vessel revascularization. Safety end points were TIMI major, minorand minimal bleeding events.Results: Between the two groups, age, sex, weight index, the proportion of high bloodpressure, smoking, stroke, prior myocardial infarction and the DES length and diameterwere not significantly different (P>0.05). At30days, attenuation of HPR was morefrequently 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 two-year follow-up were similar between the two groups (1.0%Vs4.0%, p=0.08). The rate of cardiac death (0.5%vs2.0%), nonfatal myocardial infarction(0.5%vs1.0%) and ischemic stroke (0.0%vs1.0%) were not significantly differentbetween the two groups (P>0.05). Patients in the intensive group had lower rates ofischemia driven target-vessel revascularization (2.0%vs8.0%, P=0.027) andrecurrent angina (8.5%vs.20.0%, P=0.008) compared with those of standard group.The intensive group compare with the standard group incidence of major(0.5%vs1.0%,p=0.616), minor(0.5%Vs0%, p=0.479) and minimal bleeding (6.5%vs6.0%，P=0.867).Conclusions: Intensive antiplatelet therapy with high maintenance clopidogel and/oradditional cilostazol is effective in attenuating HPR, decreasing incidences of ischemiadriven target vessel revascularization and recurrent angina, not at a price of excessiverisk of bleeding, in patients with ACS undergoing coronary stenting. However, theclinical benefits of reducing the risk of major ischemic events (cardiac death,myocardial infarction, stroke) were not observed in the present study.