A large network meta-analysis has found “little evidence” to suggest that any of the commonly used NSAIDs or COX 2 inhibitors are safe in terms of cardiovascular risk. In a paper published in BMJ, Sven Trelle and colleagues analyzed data from 31 trials in which patients receiving an NSAID were compared to another NSAID or placebo. Rofecoxib was associated with the highest risk of MI while naproxen appeared to be the safest of the agents studied. The authors concluded that “options for the treatment of chronic musculoskeletal pain are limited and patients and clinicians need to be aware that cardiovascular risk needs to be taken into account when prescribing.”
In an accompanying editorial, Wayne Ray writes that the limitations of the meta-analysis mean the results “should be interpreted with caution.” Although naproxen appears to be the safest agent it may require the concomitant use of a gastroprotective agent. Ray writes that “drugs for symptomatic relief must be evaluated with regard to the target symptoms as well as less frequent yet serious adverse effects. NSAIDs are not an ideal treatment with respect to efficacy or safety.”
Here is the BMJ press release:
Common painkillers linked to increased risk of heart problems
Research: Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis
Editorial: Cardiovascular safety of NSAIDs
Commonly used painkillers for treating inflammation can increase the risk of heart attacks and strokes, according to an analysis of the evidence published on bmj.com today.
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 In 2004, the COX-2 inhibitor rofecoxib was withdrawn from the market after a trial found that the drug increased the risk of cardiovascular disease.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.
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