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.”

One Response to “Excess Risk for Cardiac Events Associated with Dabigatran”

  1. William DeMedio, MD says:

    A new drug that can’t be reversed, can’t be monitored, is subject to decomposition if the bottle cap is left loose by the frail elderly, is taken BID, and potentially increases the risk of bleeding certainly warrants careful post marketing surveillence. I am not suprised to see an increase in MI with this drug. I had reservations about it when it was “sold” at the ECC, please see my earlier posts. How much post marketing surveillence is needed until it is removed from the market? Perhaps I should state it in another way, that is, should we ethically wait and see if the risk of death is higher with this in the post marketing arena or should we reserve it for select groups of patients i.e. the warfarin intolerant only. I have only given it to those who were aware of the risk/benefit ratio, were deemed highly compliant, and had some issue regarding not being able to take warfarin. So far I have seen no MI or deaths. The story might be different if I used it more liberally. I am still waiting to find out if the new emporor is wearing anything. My view is still obscured by the need for post marketing data.

    Competing interests pertaining specifically to this post, comment, or both: