Underreporting of cardiovascular events in the rofecoxib Alzheimer disease studies
American Heart Journal, 07/06/2012
Clinical Article
Madigan D et al. – Intention–to–treat analysis of placebo–controlled studies of rofecoxib for Alzheimer disease demonstrated that the drug produced a significant increase in confirmed CVT deaths nearly 40 months before it was removed from the market. By contrast, published analyses of these trials were restricted to on–treatment analyses (ending 14 days after cessation of treatment) that did not reveal this risk. Intention–to–treat analyses of clinical trial data can reveal important information about potential drug risks and should be performed routinely and reported in a timely manner.
Methods- Using an intention–to–treat analysis of adjudicated CVT deaths, authors analyzed detailed patient–level data collected during 3 randomized placebo–controlled trials of rofecoxib versus placebo that had been designed to define the drug's possible role in the prevention or treatment of Alzheimer disease.
- All trials had been completed by April 2003.
- In the 3 studies combined, the data indicated that rofecoxib more than tripled the risk of confirmed CVT death (risk ratio = 3.57 [1.48–9.72], P = .004).
- This finding reached the P < .05 level of significance by June 2001.
