Non-steroidal anti-inflammatory drugs and cardiac failure: meta-analyses of observational studies and randomised controlled trials

Eur J Heart Fail. 2008 Nov;10(11):1102-7. doi: 10.1016/j.ejheart.2008.07.013. Epub 2008 Aug 29.


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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Arthritis / drug therapy*
  • Heart Failure / chemically induced*
  • Humans
  • Observation / methods*
  • Randomized Controlled Trials as Topic / methods*
  • Risk Factors


  • Anti-Inflammatory Agents, Non-Steroidal