January 9th, 2012
Excess Risk for Cardiac Events Associated with Dabigatran
Compared with control treatment, dabigatran (Pradaxa) is associated with a higher risk for cardiac events, according to a new meta-analysis published online in the Archives of Internal Medicine.
Ken Uchino and Adrian Hernandez analyzed data from seven clinical trials comparing dabigatran with warfarin, enoxaparin, or placebo in 30,514 patients. The rate of myocardial infarction (MI) or acute coronary syndrome (ACS) was significantly higher in the dabigatran groups than in the control groups:
- dabigatran: 1.19% (237/20,000)
- controls: 0.79% (83/10,514)
- OR 1.33, CI 1.03-1.71, p = 0.03
The results were similar when different analyses were performed, including the exclusion of short-term trials and revised results from the RE-LY trial. The authors note that the RE-LY trial had a dominant effect on the meta-analysis, contributing 59% of the cohort and 74% of the events in the analysis.
Uchino and Hernandez conclude that “the overall benefit and risk balance of dabigatran use appears to be favorable in patients with AF because of reduction in ischemic stroke,” but that its cardiac risk “should be investigated further, especially if it is used in populations at high risk of MI or ACS.”
In an accompanying editorial, Jeremy Jacobs and Jochanan Stessman write that the problem highlighted by the meta-analysis is part of a much-larger problem:
A far wider issue of perhaps deeper concern is the enthusiasm—nearly to the level of euphoria—to embrace the new, which must be restrained by the old aphorism: primum non nocere.
In an editor’s note, Rita Redberg writes that several concerns about dabigatran have been raised since the drug’s approval, highlighting “the importance of continued collection and analysis of data after drug approval.”