NSAIDs similar to COX-2 inhibitors in raising risk of atherothrombosis

Last Updated: 2006-06-01 19:01:09 -0400 (Reuters Health)

NEW YORK (Reuters Health) - High-dose regimens of ibuprofen or diclofenac and use of selective cyclooxygenase-2 (COX-2) inhibitors are both associated with a moderate increase in the risk of vascular events, results of a meta-analysis suggest.

Dr. Colin Baigent, from the University of Oxford in the UK, and associates identified trials published between 1966 and 2005 of at least 4 weeks' duration, comparing a selective COX-2 inhibitor to placebo or to a traditional nonsteroidal anti-inflammatory drug (NSAID). Altogether, they found 138 randomized trials involving roughly 145,000 subjects.

COX-2 inhibitor use was associated with an adverse vascular event rate of 1.2% per year versus 0.9% per year for placebo (rate ratio 1.42, p = 0.003), the investigators report in the June 3rd issue of the British Medical Journal. This corresponded to an excess of three people with a vascular event per 1000 people over a one-year period when allocated to a COX-2 inhibitor.

The difference was almost entirely attributed to an excess of MI (RR 1.86, p = 0.0003). The drugs appeared to not raise the risk of stroke or vascular death.

COX-2 inhibitors had similar rates of events compared with ibuprofen or diclofenac, but a lower incidence of stroke (RR = 0.62, p = 0.03).

However, the incidence of vascular events with a COX-2 inhibitor was increased when compared with naproxen (RR = 1.57), primarily because of the incidence of MI (RR 2.04, p = 0.0002). Again, stroke and vascular death rates were not significantly different.

Rate ratios of vascular events when NSAIDs were compared with placebo were 0.92 for naproxen, 1.51 for ibuprofen, and 1.63 for diclofenac.

Celecoxib was the only COX-2 inhibitor with sufficient data to show a trend toward a dose-dependent response. Higher doses of ibuprofen and diclofenac, but not naproxen, were also associated with an excess of vascular events.

After posing the question, "Have we lost a truly superior option" by withdrawing COX-2 inhibitors from the market? Dr. Allen F. Shaughnessy and Dr. Andrea E. Gordon answer, "Probably not," because they were "an intervention that was more popular than proved."

The editorialists, from Tufts University Family Medicine Residency in Malden, Massachusetts, maintain that "other pharmacological and non-drug options may be reasonably effective, equally safe, and less costly."

For example, they recommend misoprostol or paracetamol for treatment of pain in older individuals.

Non-drug options include exercise, as well as unloader braces and taping for knee osteoarthritis. And Dr. Shaughnessy and Dr. Gordon are not averse to trying complementary and alternative approaches for treating pain.

BMJ 2006;332:1287-1288,1302-1305.