Combination Use Of Clopidogrel And Proton Pump Inhibitors Increase Major Adverse Cardiovascular Events In Patients With Coronary Artery Disease:a Meta-analysis

Background:Published data indicated that combination use of clopidogrel and proton pump inhibitors (PPIs) may increase the incidence of major adverse cardiovascular events (MACE). This has been a highly controversial topic for years.Design:The present study was performed to evaluate whether combination therapy of clopidogrel and PPIs are associated with increased risk of MACE than with clopidogrel alone in patients with coronary artery disease.Methods:A systematic search of Medline, EMBASE, and the Cochrane Library was conducted for studies recording the occurrence of MACE in patients with exposure to concomitant use of clopidogrel and PPIs from inception up to February 2015. OR were combined using a random-effects model.Results:Patients receiving combination therapy with PPIs and clopidogrel were at significantly increased risk of MACE (OR 1.49; 95% CI 1.36-1.63). Adding a PPI to clopidogrel treatment was associated with a higher rate of MACE occurrence in rapid metabolizers (RMs,*1/*1) of CYP2C19 (OR 1.42;95% CI 1.12-1.81), but there was no obviously increased rate (OR 1.43;95% CI 0.89-2.28) in patients with 1 or 2 loss-of-function allele. The increased risk of MACE was similar in four classes of PPIs (omeprazole, lansoprazole, esomeprazole, pantoprazole), but rabeprazole(OR 1.03; 95% CI 0.55-1.95) wasn’t.Conclusions:The combination use of clopidogrel and certain types of PPIs (omeprazole, lansoprazole, esomeprazole, pantoprazole) increase the risk of MACE in patients with coronary artery disease. Only in the RMs of CYP2C19, PPIs was associated with significantly increased MACE in patients coadministered with clopidogrel.