New APPROVE data confirm vioxx cardiovascular risk

In September 2004 the APPROVe (Adenomatous Polyp Prevention on Vioxx) trial was stopped early due to concerns about increased cardiovascular mortality in patients taking the drug.  An analysis of the long-term outcomes of the patients in the trial has now been published in the Lancet.

After the early termination of the trial, all 2587 participants were followed up for at least one year after stopping treatment.  The investigators examined the incidence of non-fatal myocardial infarction and stroke, and also deaths from cardiovascular, haemorrhagic, or unknown causes.

Post-treatment cardiovascular follow-up data was available from 84% of patients and extended mortality follow-up from 95%.  Overall 59 patients had one of the prespecified events in the rofecoxib group, and 34 in the placebo group (p=0.06).  In the first year after treatmentwith rofecoxib, there was a non-significant increase in the risk of these endpoints, although the hazard ratio did not change over time.

Although the number of outcomes available for analysis in this trial was small, the two “take-home” messages from this trial are:

  • the risk associated with rofecoxib use could be seen early
  • the risk persisted over the course of a year

Nonetheless, it should be recalled that NSAID therapy is also associated with increased cardiovascular risk, and the p value in the above paper is marginal.  Therefore physicians choosing an anti-inflammatory for their patient must try to balance the risks and benefits of a chosen therapy for their patient.

  • Baron JA, Sandler RS, Bresalier RS, et al. Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial. Lancet 2008; DOI:10.1016/SO140-6736(08)61490-7.
  • Baigent C and Patrono C. Selective COX-2 inhibitors: where do we go from here? Lancet 2008; DOI:10.1016/SO140-6736(08)61491-9.

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