Dabigatran Better than Warfarin for Stroke Prevention in Atrial Fibrillation

August 30, 2009 5:27 AM CT

Just announced at the European Society of Cardiology (ESC) meeting taking place in Barcelona, and simultaneously at the web site of the New England Journal of Medicine, were the results of the Randomized Evaluation of Long-Term Anticoagulant Therapy trial. Known as the RE-LY trial, the results showed that dabigatran, a potential Coumadin® replacement that is marketed under the brand name of Pradaxa outside the U.S., is more effective than warfarin at stopping both clotting (ischemic) strokes and bleeding (hemorrhagic) strokes.

This is big news for afib sufferers awaiting a replacement for the anticoagulant Coumadin® (warfarin) because it is so difficult and time-consuming to manage. Problems include food and drug interactions, the requirement for frequent blood-testing, and the need to tweak dosage levels. In addition, being on warfarin frequently requires that patients give up activities that they love. And for some people, warfarin is so difficult to stabilize within the normal therapeutic range (INR between 2.0 and 3.0) that it becomes ineffective. In fact, in this study, as in many others, participants on warfarin were typically in this therapeutic range only two-thirds of the time.

The study, conducted at 951 centers in 44 countries, involved over 18,000 non-valvular atrial fibrillation patients who had at least one other risk factor for stroke. Two doses of dabigatran, 150-mg (higher dose) and 110-mg (lower dose), each given twice daily, were compared with warfarin treatment.

Compared to warfarin, the higher dose of dabigatran reduced strokes (including hemorrhagic) by 34 percent, and there was no significant difference in the rate of major bleeding. In the lower dose, major bleeding was 20 percent lower than with warfarin. Since the higher dose had a lower risk of clots, and the lower dose had a lower risk of hemorrhage, this suggests that the dose could be tailored to the risks for an individual patient.

The higher dose was associated with a very slight additional risk of heart attack when compared to warfarin, which is likely due to warfarin being known to have a protective effect for heart attacks.

Dabigatran is much easier to use as patients don’t require any form of monitoring. It is also more effective, and has very few drug interactions. There is one important interaction with some afib drugs (i.e., verapamil, amiodarone, and quinidine) that appeared in the study to contribute to greater effectiveness of dabigatran in patients taking amiodarone, but that could also increase the risk of hemorrhage.

This news is extremely heartening since afib-related strokes are more severe and disabling than most, and half of those who have afib-related strokes die within a year.

These results are very promising for those who are unable to be stable on Coumadin, but there are a couple of downsides—dabigatran had more gastric symptoms when compared to warfarin, about 6% for warfarin and 12% for dabigatran, and as a new drug, dabigatran will likely be more costly than warfarin.

Dr. John Camm, of St. George’s University in London (UK), who was the official discussant of the results presented at ESC, stated that “dabigatran seems not to be merely a superior therapy, but we must probably regard this drug as a stimulus to a paradigm change in the antithrombotic management of atrial fibrillation.”

He did, however, raise some concerns:

  • What is the impact on the elderly?
  • Is it of concern that there isn’t an antidote to dabigatran?
  • Should we change back to warfarin if we need to cardiovert a patient?

Also of particular interest is that the reporting of these results at ESC seems to have been the first major push of a manufacturer in the afib-drug space, maybe even in the whole pharma space, into social media in conjunction with the release of study findings. Boehringer Ingelheim, the manufacturer of dabigatran, used Twitter to tweet the results in real-time as they were presented at ESC, and simultaneously announced a new Stroke Prevention channel on You Tube with videos of interest to patients and physicians.

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