Lack Increased Evidence Of Cardiovascular Events In Patients Receiving Clopidogrel With Proton-Pump Inhibitors: A Meta-Analysis And System Review

Recently, cardiologists raised concerns about the adverse cardiovascular outcomes meta-analysis to further evaluate the cardiovascular effect in patients receiving clopidogrel, with and without concomitant treatment with proton pump inhibitors. A multitude of studies published up to July 2017 that investigated the association of concomitant therapy of proton pump inhibitor and clopidogrel in patients with cardiovascular effects were collected from MEDLINE, Cochrane, EMBASE, Chinese Biomedical Literature Database (CBM), and the conference proceedings from important cardiology and gastroenterology meetings. To ensure the rigor of the research, we only included original studies published in English and Chinese. This meta-analysis was performed with the random-effect or fixed-effect models according to the presence or absence of significant heterogeneity. A total of 9 placebo-control RCTs were involved in this study. A total of 22,890 patients aged 40 years or older were available for analyses. Among the included studies, three studies were from multi-country, one study was in American and Canada; five studies were from Asian. The number of participants ranges from 30 to 9191, including men and women. The types of PPI included omeprazole, lansoprazole, pantoprazole, esomeprazole, and rabeprazole. Our meta-analysis of the studies assessing PPIs as a class compared with placebo showed no difference in composite ischemic endpoints, all-cause mortality, nonfatal MI, stroke, despite a reduction in upper gastrointestinal bleeding with omeprazole (RR 1.06, 95% confidence interval [CI] 0.95-1.18; P=0.27, with heterogeneity among trials (I-2=57%). We did subgroup analysis, pooling data of five RCTs from Asia showed no increased risk of MACE in patients administered PPIs with clopidogrel and aspirin (RR 0.81, 95% confidence interval [CI] 0.58-1.13; P=0.21). There was no statistical heterogeneity among the five subgroup studies (I-2=0%). At present, data from pharmacokinetic and pharmacodynamics studies have indicated that there might be an adverse interaction between clopidogrel and proton pump inhibitor. Therefore, the clinical validity or possible relevance to the hypothesized the interaction of clopidogrel and PPI need further investigation and discussion.