Non-Steroidal Anti-Inflammatory Drugs and Cardiac Failure: Meta-Analyses of Observational Studies and Randomised Controlled Trials

AIMS: To determine the risks of cardiac failure with non-steroidal anti-inflammatory drugs (NSAIDs) and the specific risks with Cox-2 specific NSAIDs (COXIBs). METHODS: We performed meta-analyses examining the risks of developing cardiac failure in observational studies and in randomised controlled trials (RCTs) involving patients with arthritis and non-rheumatic disorders. Electronic databases and published bibliographies were systematically searched (1997-2008). RESULTS: Five case-control studies (4657 patients, 45,862 controls) showed a non-significant association between NSAIDs and cardiac failure in a random effect model (odds ratio (OR) 1.36; 95% CI 0.99-1.85). Two cohort studies (27,418 patient years, 55,367 control years) showed a significant risk of cardiac failure with NSAIDs (relative risk 1.97; 95% CI 1.73-2.25). Six placebo-controlled trials (naproxen, rofecoxib and celecoxib) in non-rheumatic diseases (15,750 patients) showed more cardiac failure with NSAIDs (Peto OR 2.31; 95% CI 1.34, 4.00). Six RCTs comparing conventional NSAIDs and COXIBs in arthritis (62,653 patients) showed no difference in cardiac failure risk (Peto OR 1.14; 95% CI 0.85-1.53). CONCLUSION: Observational studies and RCTs all show that NSAIDs increase the risk of cardiac failure. Overall risks are relatively small and are similar with conventional NSAIDs and COXIBs. Pre-existing cardiac failure increases risk.