Intended for healthcare professionals


Rofecoxib caused excess heart disease

BMJ 2005; 330 doi: (Published 27 January 2005) Cite this as: BMJ 2005;330:212
  1. Susan Mayor
  1. London

The COX 2 (cyclo-oxygenase-2) inhibitor rofecoxib (Vioxx) could have caused an estimated 88 000-140 000 excess cases of serious coronary heart disease in the United States since its launch in 1999, says a study published this week. The drug was withdrawn in September last year after being linked to increased cardiac deaths (BMJ 2004;329: 816).

The study analysed a cohort of all patients age 18-84 years receiving health care from a managed care organisation, Kaiser Permanente, in California, who were treated with a non-steroidal anti-inflammatory drug between 1 January 1999 and 31 December 2001. Just under a million of the patients had been treated with ibuprofen, about 435 000 with naproxen, 40 000 with celecoxib, and 27 000 with rofecoxib. Each person whose condition was coded as serious coronary heart disease—defined as acute myocardial infarction and sudden cardiac death—was matched with four controls based on age, sex, and health plan region.

Results showed that 8143 cases of serious coronary heart disease—including 2210 (27%) fatal cases—occurred during 2 302 029 person years of follow up. People taking rofecoxib (all doses) had a 34% higher chance of coronary heart disease (adjusted odds ratio 1.34, 95% confidence interval 0.98 to 1.82, P=0.066) when compared with those taking other non-steroidal anti-inflammatory drugs.

Coronary heart disease was nearly 1.5 times more likely (1.47, 0.99 to 2.17, P=0.054) among people currently taking standard dose rofecoxib (‘' 25 mg/day) compared with those currently taking celecoxib and was 3.6 times more likely (3.58, 1.27 to 10.11, P=0.016) among high dose (>25 mg/day) users.

The study, whose findings have been published online in the Lancet (, also found that people taking naproxen had a 14% increased risk of coronary heart disease (1.14, 1.00 to 1.30,P=0.05) compared with other non-steroidal anti-inflammatory drugs, in contrast with previous studies that had suggested that naproxen protected against coronary heart disease.

The study concluded that rofecoxib increased the risk of serious coronary heart disease compared with celecoxib and that naproxen did not protect against serious coronary heart disease.

The lead author, David Graham from the Office of Drug Safety at the US Food and Drug Administration, Rockville, Maryland, said: “An estimated 88 000-140 000 excess cases of serious coronary heart disease probably occurred in the United States over the market life of rofecoxib. The US national estimate of the case-fatality rate (fatal acute myocardial infarction plus sudden cardiac death) was 44%, which suggests that many of the excess cases attributable to rofecoxib use were fatal.”

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