Aims We aimed to determine efficacy and safety of clopidogrel only vs. clopidogrel added PPIs in the treatment of patients with percutaneous coronary intervention.
Methods A systematic search of MEDLINE, EMBASE, and Cochrane Library was conducted for studies recording the occurrence of MACEs in patients with exposure to concomitant use of clopidogrel and individual PPIs up to October 2019. Adjusted ORs or HRs for MACEs were combined using a random-effects model.
Results We identified ten studies comprising 75689 patients. The adjusted ORs or HRs for the composite of cardiovascular or all-cause death, myocardial infarction, and stroke were reported in 2 RCTs, 2 posthoc analyses of participants in RCTs, and 10 observational studies with data on individual PPIs. Random-effects meta-analyses of the 14 studies revealed an increased risk for MACEs for those taking omeprazole (HR 1.31; 95% CI 1.22-1.39), lansoprazole (HR 1.15; 95% CI 1.06-1.24), or pantoprazole (HR 1.37; 95% CI 1.28-1.45), or esomeprazole (HR 1.28; 95% CI 1.20-1.37) compared with patients on no PPI. This association was not significant for rabeprazole (HR 1.16; 95% CI 0.98-1.39). For further validation of the results, we repeated the entire analysis, excluding the study reporting adjusted HRs only. Moreover, there were no significant changes for the summary OR estimates for any of the individual PPIs or overall PPI effect estimates. The increased risk of MACEs was similar in 4 classes of PPIs (omeprazole, lansoprazole, esomeprazole, and pantoprazole), but rabeprazole (OR: 1.36; 95% CI: 0.93-1.98) was not. Sensitivity analyses for the coronary artery disease population (acute coronary syndrome versus mixed) and exclusion of a few studies due to heterogeneity of reported results didn´t have a significant influence on the effect estimates for any PPIs.
Conclusions Although the results for rabeprazole were not robust, it was the only PPI that did not yield a significantly increased risk of MACEs.
