An Update on Dabigatran and MI Risk
Welcome, dear colleagues. My name is Christoph Diener. I am a neurologist from the University of Essen in Germany. Today's topic is atrial fibrillation, dabigatran, and the risk for myocardial infarction.

You are all aware that we have a new drug, dabigatrin, for the prevention of stroke in people with atrial fibrillation. Dabigatran has been investigated in 2 doses (110 mg and 150 mg twice daily) and compared with warfarin. The higher dose [was found to be] statistically significantly superior to warfarin for preventing stroke, and the lower dose was [found to be] equivalent. In the United States, only the high dose is approved, and in the rest of the world both doses are approved.

Now, in the January 9 online Archives of Internal Medicine, Uchino and Hernandez published a meta-analysis of the rate of myocardial infarction in all patients who ever underwent a study with dabigatran, including those for the prevention of deep vein thrombosis, the prevention of stroke in atrial fibrillation, [acute venous thromboembolism, and acute coronary syndrome]. They analyzed 7 trials with 30,000 patients altogether, and they found a rate of myocardial infarction of 237 in 20,000 treated patients in the active arm (1.19%), and 83 in 10,514 controls (0.79%). This translates to an increased risk and is statistically significant.

At about the same time, Hohnloser and colleagues published the subgroup analysis of myocardial infarction from the [Randomized Evaluation of Long-Term Anticoagulant Therapy (RELY)] trials online in Circulation. They observed the rate of 0.82% per year for the low dose of dabigatran, 0.81% per year for the high dose [of] dabigatrin, and 0.64% per year for warfarin. This is a hazard ratio of 1.29, which is not statistically significant. The subgroup of patients who already had a myocardial infarction or coronary heart disease did not have an increased risk of myocardial infarction when treated with dabigatran.

How do we translate these seemingly contradictory results into our clinical practices, and more important, is it unsafe to treat patients with atrial fibrillation and myocardial infarction with dabigatran? I think the clear answer is no. We have to consider the absolute numbers we will see when we treat patients with dabigatran. I will give you an example: The absolute number of myocardial infarction was 98 in the low dose of dabigatran, 97 in the high dose, and 75 with warfarin. This is an absolute difference of 22 myocardial infarctions in a study that had more than 20,000 patients.

Let us consider another serious adverse event, which is intracranial bleed. There were 27 intracranial bleeds with the low dose of dabigatran, 36 with the high dose, and 87 with warfarin. This is an absolute difference [of] 51, if we consider the high dose of dabigatrin. We also have to consider the mortality of the events. The mortality of myocardial infarction was about 10%, and the mortality of intracranial bleeds was about 45%.

Now, let us look at how many people died taking dabigatran instead of warfarin in the RELY trial. Two patients died because of myocardial infarction, but 23 more patients died in the warfarin group because of intracranial bleeds.

I think it is clear that dabigatran does not cause myocardial infarctions, but perhaps warfarin is able to prevent myocardial infarction. The absolute difference is so small in the RELY study that I do not think we really have to be worried that dabigatran might cause myocardial infarction.

Dear colleagues, I am Christoph Diener, a stroke neurologist from the University of Essen in Germany. Thank you for listening.