Clinical And Experimental Study About Influence Of Proton Pump Inhibitors On The Effectiveness Of Clopidogrel

Objective:(1)To assess an association between use of proton-pump inhibitors (PPIs) in combination with clopidogrel and an increased risk of cardiovascular events in elder patients with acute coronary syndrome (ACS).(2)To investigate the influence of PPIs on the antithrombotic efficacy and antiplatelet action of clopidogrel in rat models of arterial thrombosis.Methods:(1)Retrospective cohort study of 109 patients with ACS taking clopidogel after discharge from Huashan Hospital between June,2007 and May,2010. They were assigned to case group with PPIs and control group without PPIs. Primary end points were the major adverse cardiac events(MACE) and second end points were all-cause mortality, rehospitalization for ACS,myocardial infarction, cardiac death, target vessel revascularization(TVR).We assessed the risk of adverse outcomes associated with concomitant use of clopidogrel and PPIs.(2) Sixty male Sprague-Dawley rats were randomly divided into six groups:concomitant use of clopidogrel and PPIs (omeprazole of high dose, omeprazole of low dose,esomeprazole, pantoprazole), use of clopidogrel without PPIs,normal control group. Rats model of carotid arterial thrombosis were induced by FeC13 Arterial thrombus weight,ADP induced platelet aggregation, phosphorylation of vasodilator-stimulated phosphoprotein(VASP) were measured to compare the influence of PPIs on the effectiveness of clopidogrel.Results:(1)There were no significant difference in the incidence of major adverse cardiac events(major adverse cardiac events) between patients with PPIs and without PPIs (36.7%vs.48.3%,P>0.05). Comparing the incidence of second end points in patients using clopidogrel alone,the incidence of all-cause mortality (4.1%vs.16.7%), rehospitalization for ACS (32.7%vs.38.3%),myocardial infarction (8.2%vs.20.0%), cardiac death (2.0%vs.6.7%),target vessel revascularization (4.1%vs.5.0%) in patients with concomitant use of clopidogrel and PPIs were not significantly different (P> 0.05). No association existed between PPIs use and risk of the primary end points for elderly treated with clopidogrel (AHR1.10,95%CI:0.56-2.19).Use of clopidogrel and PPIs was not associated with an increased risk of all-cause mortality (AHR0.49,95% CI:0.07-3.46), rehospitalization for ACS (AHR1.28,95%CI:0.62-2.65), myocardial infarction (AHR 0.59,95%CI:0.16-2.15), cardiac death (AHR0.39,95%CI:0.04-3.85), target vessel revascularization(AHR1.23,95%CI:0.17-8.70).(2)There was no statistical difference in thrombus weight,platelet aggregation and VASP-P between concomitant use of clopidogrel with PPIs (omeprazole, esomeprazole, pantoprazole) and use of clopidigrel without PPIs (P>0.05). Different PPIs in combination with clopidogrel had little variance among thrombus weight, platelet aggregation and VASP-P, but had not statistical difference (P>0.05).Different doses of omeprazole had no significant statistical difference in thrombus weight,platelet aggregation,VASP-P comparing with non-PPIs group (P>0.05).But thrombus weight, platelet aggregation, VASP-P in high dose of omeprazole were higher than in low dose of omeprazole (P<0.05).Conclusion:Co-administration of PPIs and clopidogrel would not increase the risk of cardiovascular events in elderly with ACS. Different PPIs had no influence on the antithrombotic efficacy and antiplatelet action of clopidogrel.PPIs could be used in combination with clopidogrel when clinically indicated, except high dose of omeprazole.