Published online 3 May 2006 | Nature | doi:10.1038/news060501-4


Vioxx may trigger heart attacks within days

Canadian study shows early onset of painkiller's side-effects.

Some painkillers might promote the formation of artery-clogging blood clots.Some painkillers might promote the formation of artery-clogging blood clots.© Getty

The controversial painkiller Vioxx (rofecoxib) may cause heart attacks within just two weeks of starting the drug treatment, a study of Canadian patients claims.

The finding could influence the outcome of the many thousands of lawsuits filed against Vioxx manufacturer Merck, because it suggests that the once-popular arthritis drug could have contributed to a heart attack or stroke even among patients who took it for very brief periods.

Vioxx was pulled from the market in 2004 after a large clinical trial showed that taking the drug for 18 months nearly doubles the risk of heart attack and stroke1. There has been intense medical and legal debate about whether these problems actually kick in much earlier.

Linda Lévesque of McGill University in Montreal, Canada, and her colleagues tackled this question by scouring the computerized health records of 125,000 Quebec residents aged 66 or older. They identified people who had taken Vioxx and the related drug Celebrex (celecoxib), and examined the frequency and time at which these people suffered heart attacks.

High risk

The team found that people taking the drug were 67% more likely to suffer a heart attack in the two weeks after getting their first Vioxx prescription, compared with those who did not take it.

Nearly one in four of those who eventually had a heart attack, during the two and a half years that they were followed, did so within a fortnight of starting the drug treatment. The risk then tapered off, and their odds returned to normal within a month of stopping the treatment.

Overall, Vioxx users were around 17% more likely to suffer a heart attack over the two and a half years, Levesque found. The results, published in the Canadian Medical Association Journal (CMAJ) 2, show that users of Celebrex were not at any increased risk.

Merck representatives have pointed out that this is an observational study, rather than a randomized clinical trial such as the one showing an 18-month period of concern.

The result could be bad news for Merck, which has so far had mixed results from lawsuits that have come to trial. In April, a Texas jury ruled that the company should pay damages to the family of a man who died of a heart attack after taking the drug for one month. Merck has said it will appeal this decision.

Early days


Other studies have also hinted that Vioxx might cause cardiovascular problems early on. "It is completely consistent with what we know about Vioxx," says Dan Solomon at Brigham and Women's Hospital, Boston, Massachusetts, who has also published data that side-effects arise from day one. The new investigation helps to pinpoint the time at which these risks are greatest.

Scientists already know that the drug, which blocks the cyclooxygenase-2 (COX-2) enzyme, acts within hours to ease pain and inflammation. So to some, it is no surprise that it could also start working immediately in the arteries to trigger cardiovascular problems, perhaps by promoting the formation of artery-clogging blood clots, although the exact mechanism is not known.

Lévesque now wants to figure out what distinguishes those people who suffer side-effects, such as whether they are already susceptible to heart disease. "We now need to identify who those people are," Levesque says, so that doctors can identify beforehand who might be at highest risk from related painkillers.

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  • References

    1. Bresalier R.S., et al. N. Engl. J. Med., 352. 1092 - 1102 (2005). | Article | PubMed | ISI | ChemPort |
    2. Levesque L., Brophy M. J.& Zhang B. Can. Med. Assoc. J., 174. doi:10.1503/cmaj.051679 (2006).