New study evaluates cardiovascular risk and safety of NSAIDs

The safety of nonsteroidal anti-inflammatory drugs (NSAIDs), a cornerstone of pain management for osteoarthritis and other conditions, has been a subject of concern since the inception of these drugs. The British Medical Journal has published a new study, which analyzed 31 randomized controlled trials comparing the cardiovascular safety of any NSAID with placebo or other NSAIDs.

The data included 116,429 patients followed for more than 115,000 patient years. NSAIDs evaluated were: naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, and lumiracoxib. 

Authors reported, “While uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms.” However, they identified naproxen to be the least harmful of the drugs studied.

The primary outcome was myocardial infarction (MI); secondary outcomes included stroke, death from cardiovascular disease, and death from any cause.

Interventions and outcomes were compared for MI from 29 trials with 554 accumulated events. Evidence was lacking with 3 drugs (naproxen, diclofenac, etoricoxib) for an increased risk of MI compared with placebo; all other drugs in the study were reported “to be associated with an increased risk compared with placebo.”

Data for stroke included 26 trials with 377 accumulated events. “All drugs seemed to be associated with an increased risk compared with placebo.”

Analysis of cardiovascular death included 26 trials with 312 accumulated events, which “accounted for 46% of all deaths.” All drugs, except naproxen, were reported to show some evidence for an increased risk in cardiovascular death when compared with placebo.

On overall mortality, 28 trials with 676 accumulated events “contributed to death from any cause.” All of the drugs “seemed to be associated with risks of death from any cause when compared with placebo.”

Unlike results from observational evidence, which, the authors said, “is likely to be affected by confounding by indication,” this study, they believe, “provides the best available evidence on the safety of this class of drugs.”

The study concluded that cardiovascular risk needs to be taken into account when prescribing any NSAID.