Non-steroidal anti-inflammatory drugs and risk of heart failure exacerbation: A systematic review and meta-analysis

Background: The association between exacerbation of heart failure (HF) and use of non-steroidal anti-inflammatory drugs (NSAIDs) has long been recognized but the data on this adverse effect are limited.

Methods: To further characterize this possible association, we conducted a systematic review and meta-analysis of observation studies that reported odds ratio, relative risk, hazard ratio or standardized incidence ratio comparing risk of exacerbation of HF in patients with pre-existing HF who took NSAIDs versus non-users. Pooled risk ratios (RR) and 95% confidence intervals for conventional NSAIDs, celecoxib and rofecoxib were calculated using random-effect, generic inverse variance method.

Results: Six studies were identified and included in our data analysis. Use of conventional NSAIDs was associated with a significantly higher risk of development of exacerbation of HF with the pooled RR of 1.39 (95% CI 1.20-1.62). Elevated risk was also observed among celecoxib and rofecoxib users (RR 1.34, 95% CI 0.98-1.85 and RR 2.04, 95% CI 1.68-2.48). The pooled RR of rofecoxib was significantly higher than conventional NSAIDs (p=0.02).

Conclusion: Use of NSAIDs is associated with an increased risk of HF exacerbation among patients with pre-existing HF. The excess risk was approximately 40% for conventional NSAIDs and celecoxib. The highest risk was observed among rofecoxib users.