Over-the-counter painkillers, used 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inhibitor rofecoxib was withdrawn from the market after a trial found that the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.