Dabigatran associated with increased risk of acute coronary events


The anticoagulant dabigatran (Boehringer Ingelheim’s Pradaxa) is associated with an increased risk of myocardial infarction or acute coronary syndrome in a broad spectrum of patients when tested against some other medicines, according to a study published online by the Archives of Internal Medicine (one of the JAMA/Archives journals).

Dabigatran etexilate was approved by the European Medicines Agency in 2008 for prevention of venous thromboembolism (VTE) in adults who have undergone total hip or knee replacement and by the US Food and Drug Administration in 2010 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation, the authors write as background in the study. An original trial suggested a small increased risk of myocardial infarction with the use of dabigatran compared to warfarin in patients with atrial fibrillation.

Ken Uchino and Adrian V Hernandez, Cleveland Clinic in Ohio, USA, searched the medical literature for randomised controlled trials of dabigatran that reported on myocardial infarction or acute coronary syndrome as secondary outcomes. Seven trials were selected, involving 30,514 participants, for their meta-analysis.

The trials they included were: two studies of stroke prophylaxis in atrial fibrillation, one in acute venous thromboembolism, one in acute coronary syndrome and three trials or short-term prophylaxis of deep venous thrombosis in joint replacement. The control groups included administration of warfarin, enoxaparin or placebo.

“Dabigatran was significantly associated with a higher risk of myocardial infarction or acute coronary syndrome than that seen with agents used in the control group” (dabigatran, 237 events of 20,000 [1.19%] vs. control, 83 events of 10,514 [0.79%]), the researchers write.

They note the risk of myocardial infarction or acute coronary syndrome was similar when using revised results of a previous trial and after the exclusion of short-term trials. The authors comment that they used several meta-analytic methods and association measures and the results were consistent.

“Although the relative risk increase was 33%, the absolute risk increase was very small, at 0.27%,” they write. They suggest that while dabigatran might not directly increase the risk of myocardial infarction, it may lack the beneficial effects that warfarin and aspirin have in myocardial infarction prevention. They note they do not know the pharmacologic mechanism that may result in dabigatran increasing the risk of myocardial infarction or acute coronary syndrome.

“The overall benefit and risk balance of dabigatran use appears to be favorable in patients with atrial fibrillation because of reduction in ischaemic stroke. However, the cardiac risk of dabigatran should be investigated further, especially if it is used in populations at high risk of myocardial infarction or acute coronary syndrome,” the authors conclude.