Cardiovascular and Gastrointestinal Safety of NSAIDs: A Systematic Review of Meta-Analyses of Randomized Clinical Trials

As part of the Safety of Non-Steroidal Anti-Inflammatory Drugs (SOS) Project, we reviewed the incidence of cardiovascular (CV) and gastrointestinal (GI) events associated with the use of this category of drugs. We collected data from published meta-analyses (MAs) of clinical trials of nonsteroidal anti-inflammatory drugs (NSAIDs). The Medline, Cochrane, ISI, and SCOPUS databases were systematically searched for MAs of NSAID clinical trials that could potentially contain data on adverse incidents such as myocardial infarction (MI), cerebrovascular events (CeVs), stroke, thromboembolic events (ThEs), heart failure (HF), gastrointestinal bleeding (GIB), and perforation, ulcer, and bleeding (PUB). From 1,733 identified references, 29 MAs were selected for the review. This allowed 109 estimations of incidence rates of CV adverse events and 26 estimations of incidence rates for GI adverse events. No data were found on hemorrhagic stroke or LGIB. Coxibs were studied in more MAs than traditional NSAIDs were (21 MAs for coxibs vs. 7 for traditional NSAIDs; one meta-analysis studied both). Many NSAIDs were not considered in any of the MAs. Our systematic review of MAs included information on the incidence of CV and GI events and identified important knowledge gaps regarding, in particular, the CV safety of traditional NSAIDs.