The drugs include traditional non-steroidal anti-inflammatory drugs (NSAIDS) as well as new generation anti-inflammatory drugs, known as COX-2 inhibitors. Researchers published in British Medical Journal a comprehensive analysis of all randomized controlled trials comparing any NSAID with other NSAIDs or placebo. They included 31 trials and 116,429 patients taking seven different drugs (naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib) or placebo to provide a more reliable estimate of the cardiovascular risks of these drugs than previous studies. Overall, the number of harmful outcomes that could be compared for placebo versus treatment was low. In 29 trials there was a total of 554 heart attacks; in 26 trials there were 377 strokes, and in 28 trials there were 676 deaths. However, the researchers did find that, relative to placebo, the drugs carried important risks.
For instance, compared with placebo, rofecoxib and lumiracoxib were associated with twice the risk of heart attack, while ibuprofen was associated with more than three times the risk of stroke. Etoricoxib and diclofenac were associated with the highest (around four times) risk of cardiovascular death. Naproxen appeared least harmful in terms of cardiovascular safety among the seven analysed preparations.
The researchers concluded that although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug. An accompanying editorial says these cardiovascular risks are worrying because many patients have both cardiovascular disease and musculoskeletal disease, and suggests that it is time for an evaluation of a broader range of alternatives.