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08-06-2010 | Cardiology | Article

NSAID use in healthy people linked to increased CVD risk


Free abstract

MedWire News: Research from Denmark indicates that use of certain non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased cardiovascular disease (CVD) risk even among healthy people.

In particular, the study found that the commonly prescribed nonselective NSAID diclofenac increased CVD risk as much as the selective cyclo-oxygenase (COX)-2 inhibitor rofecoxib, which was withdrawn from the market in 2004 due to cardiovascular safety concerns. Diclofenac does have high COX-2 inhibiting selectivity, the authors point out.

Most previous evidence demonstrating an increased CVD risk from NSAIDs has come from studies in populations already at increased risk for CVD or with established disease.

To investigate the CVD risk associated with their use in a healthy population, a team led by Emil Loldrup Fosbøl (Copenhagen University Hospital Gentofte) linked individual data from Danish administrative registers to identify a cohort of 1,028,437 individuals, 44.7% of whom claimed at least one prescription for NSAIDs between 1997 and 2005.

None of the participants had been hospitalized in the 5 years prior to the prescription index date, or had any prescription claims for selected concomitant medications in the previous 2 years.

Case-crossover analysis showed that diclofenac and rofecoxib were both associated with increased risks for CVD death, at odds ratios of 1.91 and 1.66 versus no use, respectively.

The association appeared to be dose-dependent for both drugs, with a nonsignificant 1.23-fold increased risk associated with doses of diclofenac less than 100 mg and a significant 2.04-fold increased risk at doses of 100 mg or more. For rofecoxib, CVD risk was increased 1.52-fold at doses of 25 mg or less and 1.73-fold at doses over 25 mg, although neither of these associations was statistically significant.

In addition, ibuprofen use was associated with a 1.29-fold increased risk for fatal or nonfatal stroke.

In Cox proportional hazard analysis in which NSAID initiators were compared with age-, gender-, and time-matched controls, diclofenac and rofecoxib at the highest doses were associated with 1.5- and 2.8-fold increased risks for CVD death, respectively.

In line with previous studies, naproxen use was not associated with increased risk for CVD death or indeed risk for coronary death or nonfatal myocardial infarction, although it was associated with a trend towards increased risk for nonfatal or fatal stroke risk.

“Our results suggest that naproxen could be a safer alternative when NSAID treatment is required,” observe the authors.

The findings are consistent with a 2007 American Heart Association scientific statement on use of NSAIDs, excluding aspirin, for chronic pain – recommending a stepped-care approach based on the patient’s risk profile.

“I find this new study reassuring because it endorses the recommendations we made using a large body of actual clinical evidence,” commented Elliot Antman (Harvard Medical School, Boston, Massachusetts, USA), who was lead author of the statement.

“Doses examined in this new study were very similar to doses that patients are likely to encounter at the over-the-counter level and the prescription level,” he noted.

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Caroline Price

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