Non-steroidal anti-inflammatory drug-induced cardiovascular adverse events: a meta-analysis

What is known and objectiveAlthough 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. MethodsWe 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 discussionIncidence of MI was increased by rofecoxib in all comparison categories [all NSAIDs (OR: 1811, 95% CI: 1379-2378), placebo (OR: 1655: 95% CI: 1029-2661), nsNSAIDs (OR: 2155, 95% CI: 1146-4053), and COXIBs (OR: 1800, 95% CI: 1217-2662)], but was decreased by celecoxib and naproxen in the COXIB comparison [(OR: 0583, 95% CI: 0396-0857) and (OR: 0609, 95% CI: 0375-0989, respectively]. Incidence of stroke was increased by rofecoxib in comparisons with all NSAIDs and other COXIBs [(OR: 1488, 95% CI: 1027-2155) and (OR: 1933, 95% CI: 1052-3549), respectively]. Incidence of stroke was decreased by celecoxib when compared with all NSAIDs, nsNSAIDs, and COXIBs [(OR: 0603, 95% CI: 0410-0887), (OR: 0517, 95% CI: 0287-0929), and (OR: 0509, 95% CI: 0280-0925), 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: 1612, 95% CI: 1313-1981), (OR: 1572, 95% CI: 1123-2201) and (OR: 1838, 95% CI: 1323-2554), respectively]. Incidence of composite endpoint was decreased by celecoxib in the all NSAIDs and COXIBs comparisons [(OR: 0805, 95% CI: 0658-0986) and (OR: 0557, 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 conclusionThis 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.