The Pharmaceutical Journal
Vol 269 No 7219 p516
12 October 2002

This article
Reprint
Photocopy

News summary

Related websites
The Lancet (www.thelancet.com)

Long-term, high-dose rofecoxib should be avoided

Patients who start rofecoxib (Vioxx) treatment at a high dose (>25mg daily) could be at almost twice the risk of serious coronary heart disease (CHD) compared with patients who do not use non-steroidal anti-inflammatory drugs, say American researchers (Lancet 2002;360:1071).

Professor Wayne Ray of the Vanderbilt University School of Medicine, Nashville, Tennessee, and colleagues assessed occurrence of serious CHD in over 200,000 non-users of NSAIDs and in over 24,000 users of rofecoxib and over 150,000 users of other NSAIDs. They found that individuals treated with high-dose rofecoxib were 1.70 times (95 per cent confidence interval 0.98–2.95, P=0.058) more likely to have CHD than non-users of NSAIDs and 1.78 times (0.99–3.21, P=0.056) more likely to have CHD than individuals treated with celecoxib (Celebrex). These rates increased to 1.93 (1.09–3.43, P=0.024) and 2.20 (1.17–4.10, P=0.014), respectively, among new users.

The researchers found no evidence of increased risk among users of other NSAIDs or among those treated with rofecoxib at doses of 25mg daily or less.

They comment that the study has limitations, most notably that individuals taking rofecoxib could have differed from non-users of NSAIDs in their risk of serious CHD. However, the excess risk for high-dose rofecoxib persisted when a comparison was made with users of celecoxib, whose baseline characteristics were similar to those for users of rofecoxib. "Our data .. . raise serious doubts about the cardiovascular safety of [rofecoxib] at doses greater than 25mg," they conclude.

A spokeswoman for Merck Sharp & Dohme told The Journal that the company's own analyses of these data do not support the authors' conclusions. "It is important to consider the conclusions of this single observational analysis within the context of what is known about the cardiovascular safety profile of rofecoxib," she said.

She added that prospective studies comparing the incidence of serious cardiovascular events occurring in patients receiving rofecoxib with those taking NSAID comparators or placebo have not been performed.