Randomised controlled trials (RCTs) that compared cardiovascular outcomes and mortality in patients receiving clopidogrel with versus without proton-pump inhibitors (for at least 30 days) were eligible for inclusion. Case-control and cohort studies were eligible if they reported cardiovascular outcomes or mortality in patients taking clopidogrel with versus without proton-pump inhibitors. The outcomes of interest were myocardial infarction or acute coronary syndrome, all-cause mortality, and the composite outcome of major adverse cardiovascular events.
Included studies were conducted in the USA, Europe, Canada, Japan, and other parts of the world. The mean or median age ranged from 57 to 77 years, and the percentage of patients who were male ranged from 48 to 99, where reported. Patients had undergone stenting and/or percutaneous coronary intervention, had acute coronary syndrome, had serum markers of acute myocardial infarction, or were receiving clopidogrel for unreported diagnoses. A variety of proton-pump inhibitors were assessed, the main ones being omeprazole, pantoprazole, esomeprazole, lansoprazole, and rabeprazole.
Two reviewers independently assessed studies for inclusion; disagreements were resolved through consensus.