High Maintenance Dose Of Clopidogrel Influences Perioperative Platelet Activity In Patients With Acute Coronary Syndrome Selecting Percutaneous Coronary Intervention

Objective:Clopidogrel resistance in patients with acute coronarysyndrome after coronary stent intervention of acute,subacute,late and very latethrombosis and other cardiovascular events important issues,but also a hotissue of international concern.Gurbel,etc.studies have shown that anti-plateleteffect of clopidogrel is dose-dependent,given the high dose of clopidogrel caneffectively inhibit platelet aggregation.At presents,several multi-centerrandomized studies of Bonello et al have confirmed that adjusted600mgclopidogrel loading dose (≤4)can significantly inhibit platelet high reactivityso as to improve clinical overcome of patients of CR undergoingPCI.Promoted difficultly,this method can not be appliedregularly.Meanwhile,American College of Cardiology/American HeartAssociation recommend an increase in clopidogrel maintenance dosage to150mg/day in patients of ACS(Ⅱ b,C).Therefore,we aim to investigatewhether a higher clopidogrel maintenance dosage is associated with asignificant improved platelet activity after percutaneous coronary intervention(PCI) in patients with acute coronary syndrome especially inclopidogrel-resistant patients and to evaluate its efficacy and safety in ashort-term in this study.Methods:208consecutive patients admitted to Armed Police GeneralHospital Department of Cardiology were enrolled between June2011andJanuary2012.They were patients with a diagonosis of ACS who werescheduled for elective coronary angiography.Blood samples were obtained byvenipuncture of the antecubital vein respectively between6-12h after theclopidogrel600mg and at2d and5d after the start of the maintenance dose ofclopidogrel.The VASP phosphorylation analysis of blood collection was performed with BD FACSCalibur flow cytometer.According to the definitionof High Platelet Reactivity(PRI≥50%)accepted internationally which wascorrelated well with clinical prognosis of patients undergoing PCI,confirmedby several studies and ROC curve analysis,patients were divided intoClopidogrel low-response group(PRI≥50%,n=76) and controlgroup(PRI<50%,n=52).Patients within two groups were randomized toclopidogrel150mg/day(PRI≥50%,n=38vs PRI<50%,n=26) or75mg/day(PRI≥50%,n=38vs PRI<50%,n=26).Clopidogrel150mg/day wasswitched to75mg/day after one month.All patients received aspirin100mg/day.The primary endpoint:Compare PRI value7days after PCI withbaseline,evaluate whether the Platelet reactivity was improved significantly by150mg/day or not.The secondary endpoint: Observe the incidence of MACEand bleeding events1month follow-up.Results:1This prospective,randomized,contolled study was finally performed on128patients undergoing PCI with DES.We excluded80patients who did notundergo PCI with stenting (71patients who did not reach the guideline ofPCI,another9patients was suggested to receive surgery CABG).2The reduction of PRI from the baseline to the7thday after PCI between150mg/day and75mg/day subgroups was-4%in controlgroup(PRI<50%,P<0.01) and-16%in clopidogrel low-responsegroup(PRI≥50%,P=0.000),which was more remarkable in the latter.3In PRI<50%group,the compliance rate of PRI%at7d postprocedure isrespectively65%and88%in75mg/day and150mg/daysubgroups(P=0.048),they have no statistic difference. In PRI≥50%group,thecompliance rate of PRI%at7d postprocedure is respectively24%and84%in75mg/day and150mg/day subgroups(P=0.000),they have statistic difference.4During1month follow-up,in PRI<50%group,4minor bleeding in150mg/day subgroup and1minor bleeding in75mg/day subgroup occurred,not resulting in a statistically difference(15.4%vs3.8%;P=0.35),and nocardiovascular adverse events or major bleedings were recorded; In PRI≥50% group,2minor bleeding in150mg/day subgroup and1minor bleeding and2cardiovascular adverse events in75mg/day subgroup occurred, not resulting ina statistically difference（Mace0%vs5.3%,P=0.47;minor bleeding5.3%vs2.6%,P=1.0）,with no major bleedings recorded.Conclusions:1We found that150mg/day high clopidogrel maintenance dose canobviously suppress platelet reactivity by VASP phosphorylation analysis.Inhigh-risk ACS patients of PRI≥50%,increased clopidogrel maintenance dosecan make PRI reach the standard in short-term and apply in clinical easily.Inpatients of PRI≥50%,routine maintenance dose can also make PRI reach thestandard in short-term.So we can provide the basis for perioperationmedication of ACS patients.2There is a tendency that150mg/day high clopidogrel maintenance dosecan reduce MACE in ACS patients with resistant clopidogrel.3It is150mg/day high clopidogrel maintenance dose that does notincrease bleeding events in ACS patients.