Dabigatran Associated With Increased Risk Of Acute Coronary Events

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Academic Journal
Main Category: Cardiovascular / Cardiology
Article Date: 11 Jan 2012 - 8:00 PST

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A study published Online First in the Archives of Internal Medicine, one of the JAMA/Archives journals reveals that the anticoagulant dabigatran is linked to a higher risk of heart attack (myocardial infarction) or acute coronary syndrome in a wide range of patients when tested against some other medicines.

The conclusion of the study is that:

"Clinicians should consider the potential of these serious harmful cardiovascular effects with use of dabigatran."

Background information in the article states that the European Medicines Agency approved Dabigatran etexilate for the prevention of venous thromboembolism (VTE) in adults who underwent a total hip or knee replacement in 2008.

Two years later, in 2010 the U.S. Food and Drug Administration approved the drug for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). The original trial indicated that patients with atrial fibrillation on dabigatran had a small increased risk of myocardial infarction (MI) compared with patients receiving warfarin.

During their examination of medical literature for randomized controlled trials of dabigatran that contained reports on MI or acute coronary syndrome (ACS) as secondary outcomes, Ken Uchino, M.D., and Adrian V. Hernandez, M.D., Ph.D., of the Cleveland Clinic in Ohio found seven eligible trials with a total of 30,514 participants for their meta-analysis.

The eligible trials consisted of two studies of stroke prophylaxis in atrial fibrillation, one study in acute venous thromboembolism, whilst one was in ACS with three trials or short-term prophylaxis of deep venous thrombosis in joint replacement. The control groups in each trial included patients who received warfarin, enoxaparin or placebo.

They state: "Dabigatran was significantly associated with a higher risk of MI or ACS than that seen with agents used in the control group," adding that whilst 237 events occurred in 20,000 patients (1.9%) in the dabigatran group, the control group registered 83 events in 10,514 patients (0.79%).

The researchers remarked that the risk of MI or ACS was similar when using revised results of a previous trial and after the exclusion of short-term trials and point out that they used several meta-analytic methods and association measures and the results were consistent.

They write:

"Although the relative risk increase was 33 percent, the absolute risk increase was very small, at 0.27%."

They indicate that even though dabigatran may not directly raise the risk of MI, it does not match the beneficial effects that warfarin and aspirin have in preventing MI. The researchers point out that they have no knowledge of the pharmacologic mechanism that could lead to dabigatran increasing the risk of MI or ACS.

They conclude:

"The overall benefit and risk balance of dabigatran use appears to be favorable in patients with AF because of reduction in ischemic stroke. However, the cardiac risk of dabigatran should be investigated further, especially if it is used in populations at high risk of MI or ACS."

Invited Commentary: Dabigatran: Do We Have Sufficient Data?

Jeremy M. Jacobs, M.B.B.S., and Jochanan Stessman, M.D., of the Hadassah-Hebrew University Medical Center and Hebrew University-Hadassah Medical School in Jerusalem, Israel, write in an accompanying article:

"The robust finding that dabigatran is associated with increased rates of MI is alarming and emphasizes the need for continued critical appraisal of new drugs after phase 3 trials. Uchino and Hernandez have drawn our attention to the potential safety issue concerning dabigatran and the risk of MI, extracting data from the small number of available RCTs (randomized controlled trials) amidst a plethora of recent literature.

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. Only a balanced view of all high-quality data for dabigatran can permit such an assessment necessary to guide clinical decisions."

Written by Petra Rattue


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