Rofecoxib is one of the new breed of anti-inflammatories known as COX-2 (cyclo-oxygenase-2) inhibitors that are supposed to be safer than NSAIDs such as aspirin.

Aspirin and other NSAIDs (non-steroidal anti-inflammatory drugs) can cause gastric problems, such as peptic ulcers and gastrointestinal bleeding, so the COX-2 inhibitors were developed. The first were approved in the US in 1999 and, by October 2000, rofecoxib and celecoxib, another COX-2 inhibitor, had achieved sales of $3 billion. Over 100 million prescriptions for these new drugs were prepared in just 12 months.

But it seems these drugs may not be as safe as everyone thought, and they could increase the risk of heart disease. Researchers at the Cleveland Clinic in the US analysed the results of four studies involving around 16,000 arthritis patients treated with either NSAIDs or a COX-2 inhibitor. In one of the studies, patients randomly assigned to receive rofecoxib were more than twice as likely to suffer a cardiovascular event - such as a heart attack, unstable angina or a stroke - than patients given an NSAID. In all, 111 patients taking rofecoxib suffered a serious heart problem compared with 50 taking an NSAID.

In a study that compared celecoxib with an NSAID, no difference was seen in the two groups. However, patients taking the COX-2 inhibitors were also permitted to take small amounts of aspirin, which is known to reduce the risk of certain types of heart disease. In contrast, aspirin was not permitted in the rofecoxib trial.

The worry is that, if COX-2 inhibitors are only safe when taken with aspirin, then any safety advantages would be lost.

The researchers urge caution in the prescribing of these new drugs, especially to patients with a known heart risk, until their safety has been assessed in further studies (JAMA, 2001; 286: 954-9).