The drugs include traditional non-steroidal anti-inflammatory drugs (NSAIDS) as well as new generation anti-inflammatory drugs, known as COX-2 inhibitors.
The researchers say that doctors and patients need to be aware that prescription of any anti-inflammatory drug needs to take cardiovascular risk into account.
NSAIDs have been the cornerstone of managing pain in patients with osteoarthritis and other painful conditions. In 2004, the COX-2 inhibitor rofecoxib was withdrawn from the market after a trial found that the drug increased the risk of cardiovascular disease. Since then, there has been much debate about the cardiovascular safety of COX-2 inhibitors and traditional NSAIDs, which several studies have not been able to resolve.
So researchers in Switzerland performed a comprehensive analysis of all randomised 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. So the absolute risk of cardiovascular problems among people taking painkillers was low, but 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.
Although the number of cardiovascular events in the trials was low, the authors say "our study provides the best available evidence on the safety of this class of drugs." They conclude: "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.
- S. Trelle, S. Reichenbach, S. Wandel, P. Hildebrand, B. Tschannen, P. M. Villiger, M. Egger, P. Juni. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ, 2011; 342 (jan11 1): c7086 DOI: 10.1136/bmj.c7086
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