The Prevalence And Influential Factors Of Clopidogrel Resistance In Patients With Acute Coronary Syndrome

Background:Although antiplatelet therapy with a combination of clopidogrel and aspirin obviously reduces the risk of cardiovascular events in patients with acute coronary syndrome(ACS) undergoing percutaneous coronary intervention(PCI), actually a subgroup of patients still occur thrombosis complications,which implies incomplete platelet inhibition due to clopidogrel resistance.The present study explores the prevalence and influential factors of clopidogrel resistance in patients with ACS, which has very important clinical values.Objective:1.To appraise the prevalence of clopidogrel resistance in patients with ACS scheduled for PCI.2.To analyze the probable influential factors of clopidogrel resistance,to provide with evidences which reduce the risk of cardiovascular events including stent thrombosis in patients with ACS after PCI.3.To investigate the relationship between clopidogrel resistance and the recurrence of clinical ischemic events after PCI.Methods:1.The influence on platelet aggregation was studied in patients with ACS who received a conventional prescription of clopidogrel combined with aspirin.2.100 patients with ACS scheduled for PCI were enrolled.All patients were treated regularly with aspirin 100mg/d and received a loading dose of 300mg clopidogrel at least 6 hours before PCI,followed by a maintenance dose of 75mg/d.Platelet aggregation induced by ADP with a concentration of 5umol/L was measured before and 24-hour after clopidogrel intake and the inhibition of platelet aggregation(IPA) was calculated: {IPA(ΔA) was equal to the platelet aggregation before treated(Apre) minus the platelet aggregation after treated(Apost)},ΔA≤10%(including negative value) was defined to be clopidogrel resistance.According to the value ofΔA,the patients were divided into two groups:clopidogrel resistance group and clopidogrel sensitive group. 3.To analyze the probable influential factors of clopidogrel resistance.4.To observe the recurrence of clinical ischemic events in the first month after PCI.Results:100 patients with ACS scheduled for PCI were selected,the mean platelet aggregation declined significantly after clopidogrel management(pre-treatment 52.63 %±16.55%vs.post-treatment 31.93%±13.32%,p＜0.001).23 patients(23/100 cases) had clopidogrel resistance,77 patients(77/100 cases) had no clopidogrel resistance.The baseline characteristics such as age,gender,smoking history,incidence of hyperlipidemia,hypertension,diabetes mellitus and the family history of coronary artery disease(CAD) were insignificantly different between the two groups(all P＞0.05).The baseline platelet aggregation of clopidogrel resistance group was distinctly lower than clopidogrel sensitive group(38.9%±12.50%vs.56.73%±15.42%,p＜0.001).The concomitant drug use such as angiotensin converting enzyme inhibitors(ACEIs) or angiotensinⅡreceptor blockers(ARB),dihydropyridine calcium channel blockers(CCB),β-receptor blockers,diuretics,Statins,nitrates did not differ significantly between two groups(all P＞0.05).There were no significant differences between the two groups with respect to the outcomes of coronary angiography(CAG) and PCI(all P＞0.05).Logistic stepwise regression analysis showed that the baseline level of platelet aggregation was independent predictors for developing clopidogrel resistance(P＜0.05).During one month follow-up after PCI, none died of cardiovascular disease or recurred MI;there were three recurrent events in clopidogrel resistance group(including one patient occurred cerebral infarction and two recurred angina),the recurrence rate of thrombotic events is 13.04%;none thrombotic events ocurred in clopidogrel sensitive group.Conclusions:A subgroup of patients with ACS undergoing PCI does not respond to clopidogrel,which may correspond to the increasing risk of occurrence of thrombosis complications.Clopidogrel resistance could be caused by several risk factors.The most important risk factor was the baseline platelet activation;the baseline pretreatment platelet aggregation has prognostic value of clopidogrel resistance.Patients with lower pretreatment platelet aggregation have weak response to clopidogrel and will seldom get antithrombotic benefit,the mechanism of which is not very clear.This current study showed that even with combination antiplatelet therapy with aspirin and clopidogrel,there were still some patients did not benefit from it,thus resulting in the increase of recurrent ischemic events.That is,despite intensified antiplatelet therapy, they may also develop thrombotic events.So it is important to evaluate inhibition ability of clopidogrel and baseline platelet aggregation in order to identify clopidogrel resistance and may justify the treatment of those patients with an alternative antiplatelet strategy.Platelet aggregation testing may help to identify these patients who may then benefit from an alternative antiplatelet therapy.