NMA: Nonprescription Medicines Academy

Meta-Analysis Quantifies Cardiovascular, Gastrointestinal Risks of Particular NSAID Regimens

August 22nd, 2013

Although NSAIDs increase cardiovascular and gastrointestinal risks to a varying extent, the effects of different regimens in particular patients can be predicted once the baseline risks of such hazards are known, according to the results of meta-analyses designed to characterize and quantify the risks of NSAID regimens.

The meta-analyses were performed on individual participant data (or tabular data if individual participant data were not available) from randomized trials of NSAIDs, including selective COX-2 inhibitors (coxibs) as well as traditional NSAIDs. The authors identified 280 trials of NSAIDs versus placebo (124,513 participants; 68,342 person-years) and 474 trials of one NSAID versus another NSAID (229,296 participants; 165,456 person-years). The main outcomes were major vascular events (nonfatal myocardial infarction, nonfatal stroke, or vascular death); major coronary events (nonfatal myocardial infarction or coronary death); stroke; mortality; heart failure; and upper gastrointestinal complications (perforation, obstruction, or bleed).

The results of the meta-analyses showed that high-dose diclofenac has vascular risks similar to coxibs. It is possible that high-dose ibuprofen also has vascular effects similar to coxibs. High-dose naproxen appears to be associated with less vascular risk than other NSAIDs, but it is unclear whether this is true of the lower doses used most commonly in clinical practice.

Hypothetical calculations of the annual excess risks of each of the main NSAIDs (as compared with placebo) showed that among individuals at high risk (2% per annum) of major vascular events, for every 1,000 patients allocated to a year of treatment with a coxib regimen or high-dose diclofenac regimen, about seven or eight more would have a major vascular event, and two of those events would be fatal.

Lancet. 2013 May 29. [Epub ahead of print]