Rofecoxib increased composite cardiovascular outcomes compared to all NSAIDs (OR 1.612; 95% CI 1.313-1.981), while celecoxib decreased it, suggesting COX-2 selectivity may not drive CV risk.
Meta-Analysis
Does COX-2 selectivity in NSAIDs increase the risk of cardiovascular adverse events compared to non-selective NSAIDs or placebo?
This meta-analysis suggests that COX-2 selectivity as a class effect may not increase cardiovascular risk, and that previously observed risks were primarily driven by rofecoxib.
Odds Ratio: 1.612 (95% CI 1.313–1.981)
WHAT IS KNOWN AND OBJECTIVE: Although non-steroidal anti-inflammatory drugs (NSAIDs) have been studied in randomized, controlled trials and meta-analyses in an effort to determine their cardiovascular (CV) risks, no consensus has been reached. These studies continue to raise questions, including whether cyclooxygenase-2 (COX-2) selectivity plays a role in conferring CV risk. We performed a meta-analysis of current literature to determine whether COX-2 selectivity leads to an increased CV risk. METHODS: We utilized randomized, controlled trials and prospective cohort studies. We selected eight NSAIDs based on popularity and COX selectivity and conducted a search of the MEDLINE, EMBASE, and Cochrane databases. Primary endpoints included any myocardial infarction (MI), any stroke, CV death, and a combination of all three (composite CV outcomes). Twenty-six studies were found that met inclusion and exclusion criteria. Comparisons were made between all included drugs, against placebo, and against non-selective NSAIDs (nsNSAIDs). Drugs were also compared against COX-2 selective inhibitors (COXIBs) with and without inclusion of rofecoxib. RESULTS AND DISCUSSION: Incidence of MI was increased by rofecoxib in all comparison categories all NSAIDs (OR: 1·811, 95% CI: 1·379-2·378), placebo (OR: 1·655: 95% CI: 1·029-2·661), nsNSAIDs (OR: 2·155, 95% CI: 1·146-4·053), and COXIBs (OR: 1·800, 95% CI: 1·217-2·662), but was decreased by celecoxib and naproxen in the COXIB comparison (OR: 0·583, 95% CI: 0·396-0·857) and (OR: 0·609, 95% CI: 0·375-0·989, respectively. Incidence of stroke was increased by rofecoxib in comparisons with all NSAIDs and other COXIBs (OR: 1·488, 95% CI: 1·027-2·155) and (OR: 1·933, 95% CI: 1·052-3·549), respectively. Incidence of stroke was decreased by celecoxib when compared with all NSAIDs, nsNSAIDs, and COXIBs (OR: 0·603, 95% CI: 0·410-0·887), (OR: 0·517, 95% CI: 0·287-0·929), and (OR: 0·509, 95% CI: 0·280-0·925), respectively. No NSAID reached statistical significance in regard to CV death. Incidence of the composite endpoint was increased by rofecoxib when compared against all NSAIDs, placebo, and other COXIBs (OR: 1·612, 95% CI: 1·313-1·981), (OR: 1·572, 95% CI: 1·123-2·201) and (OR: 1·838, 95% CI: 1·323-2·554), respectively. Incidence of composite endpoint was decreased by celecoxib in the all NSAIDs and COXIBs comparisons (OR: 0·805, 95% CI: 0·658-0·986) and (OR: 0·557, 95% CI: 0.404-0.767), respectively. When rofecoxib was removed from the COXIBs group, no difference was found with any comparison, suggesting rofecoxib skewed the data. WHAT IS NEW AND CONCLUSION: This instead of the meta-analysis suggests that COX-2 selectivity may not play a role in the CV risk of NSAIDs. Rofecoxib was the only drug to demonstrate harm and skewed the data of the COX-2 selective group.
Gunter et al. (Mon,) conducted a meta-analysis in Cardiovascular risk. COX-2 selective inhibitors (e.g., rofecoxib, celecoxib) vs. Placebo, non-selective NSAIDs, or other COXIBs was evaluated on Composite of any myocardial infarction, any stroke, and cardiovascular death (OR 1.612, 95% CI 1.313-1.981). Rofecoxib increased composite cardiovascular outcomes compared to all NSAIDs (OR 1.612; 95% CI 1.313-1.981), while celecoxib decreased it, suggesting COX-2 selectivity may not drive CV risk.