Similar CV risk for etoricoxib and diclofenac shown
Risk of heart attack, death or stroke in arthritis patients treated with the cyclo-oxygenase-2 (COX-2) inhibitor etoricoxib is not statistically different from that in patients treated with the traditional non-steroidal anti-inflammatory drug (NSAID) diclofenac.
Data from the first large randomised controlled trial set up specifically
to study the cardiovascular safety of a COX-2 inhibitor were presented
earlier this week at an American
College of Rheumatology meeting in Washington,
at an American
Heart Association meeting in Chicago and published online
in The Lancet (13
November 2006).
The multinational etoricoxib and diclofenac arthritis long-term (MEDAL)
trial involved randomising 34,701 patients with osteoarthritis or rheumatoid
arthritis to receive etoricoxib 60mg or 90mg daily, or diclofenac 150mg
daily. Average treatment duration was 18 months.
A total of 320 patients taking etoricoxib and 323 taking diclofenac had
thrombotic cardiovascular events — with a hazard ratio of 0.95
for etoricoxib (95 per cent confidence interval 0.81–1.11) for
patients who followed the trial protocol. Overall rates of upper gastrointestinal
events — perforation, bleeding, obstruction or ulcer — were
lower with etoricoxib with a hazard ratio of 0.69 (0.57–0.83).
But complicated, life-threatening upper gastrointestinal events were
similar between the two groups.
Both doses of etoricoxib were associated with higher discontinuation
rates due to hypertension and more patients discontinued etoricoxib 90mg
due to oedema compared with those taking the non-selective NSAID.
Lead author Christopher Cannon, cardiologist at the Brigham and Women’s
Hospital in Boston, stressed the trial’s limitations — the
lack of a placebo group meant absolute cardiovascular risks with the
drugs could not be calculated.
He said: “This doesn’t answer all the questions about the
cardiovascular safety of NSAIDs by any means but it does mean we have
another big piece of the puzzle.
“When choosing a chronic pain treatment we have to take into account
thrombotic and gastrointestinal risks as well as renovascular effects
and, of course,
efficacy.” He added that he hoped guideline committees would use
the results to produce advice for clinicians on how best to individualise
treatment choices.
Diclofenac was chosen as the comparator because it is the most widely
prescribed NSAID and also because it does not interfere with the antiplatelet
effects of low-dose aspirin, unlike naproxen or ibuprofen. About a third
of patients in MEDAL were taking prophylactic low-dose aspirin.
Ernest Choy, consultant rheumatologist at King’s College Hospital,
London, commented: “These data conclusively show that etoricoxib
has the same cardiovascular risk profile as the most widely used NSAID
in the world. But it is important to put into perspective the fact that
the absolute increased risk of a CV event with an NSAID is small.”
Alzheimer’s study data Naproxen, but not celecoxib, is associated with
an increased risk for cardiovascular harm compared with placebo, suggest safety
data from a trial designed to test the two drugs as Alzheimer’s
disease treatments (PLoS Clinical Trials 2006;1[7]:e33).
The trial involved over 2,500 participants aged 70 years or older who
had a family history of Alzheimer’s disease. They were treated
with either celecoxib (200mg twice daily), naproxen (220mg twice daily)
or placebo.
Follow up was planned
for seven years but the trial was halted early, with median follow-up
times of just under two years for each treatment arm.
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