Dabigatran as effective as warfarin in preventing subsequent strokes among atrial fibrillation patients

Study highlights:

- A new anti-clotting drug proved as effective as the blood thinner currently used to prevent stroke in atrial fibrillation patients with prior stroke or transient ischemic attacks

- The lower dose of the drug dabigatran produced less risk of bleeding in the brain than warfarin did

- Dabigatran is not approved in the United States but is available in other countries to prevent blood clots after elective hip and knee replacement surgery

The drug dabigatran was as effective as the currently recommended drug – warfarin – in preventing a subsequent stroke among people with atrial fibrillation and prior stroke or transient ischemic attack – and it did so with less bleeding according to late-breaking science presented at the American Stroke Association's International Stroke Conference 2010.

Dabigatran is a member of a new class of anti-clotting drugs called direct thrombin inhibitors.

The findings come from a subset of patients who participated in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial, which tested the efficacy of the two drugs in people with irregular heart rhythm called atrial fibrillation.  Researchers enrolled RE-LY participants at 951 sites in 44 countries, including the United States.  They randomized patients to receive warfarin —adjusted to maintain the drug's therapeutic range — or to 110 mg or 150 mg of dabigatran taken twice daily for a median of two years.

In the subgroup of 3,623 patients with both a history of either stroke or transient ischemic attack (TIA), stroke or clot in other blood vessels occurred in 64 patients on warfarin (2.74 percent a year), 55 on low-dose dabigatran (2.32 percent a year) and 51 on high-dose dabigatran (2.07 percent a year).  

Neither of these differences was significant.

The rates of major bleeding events were significantly lower (32 percent less likely) in patients taking the lower dose of dabigatran compared to those taking warfarin, but it was not reduced in patients on the higher dose.

The risk of cerebral bleeds was significantly reduced with both dosages of dabigatran.  Researchers also noted that dabigatran-treated patients suffered more heart attacks than the warfarin group although the absolute difference was small.

Dabigitran has not yet been approved for use in the United States.  It is approved in other countries for the primary prevention of blood clots in patients who have undergone elective total hip or elective total knee replacement surgery.

"You can prevent stroke with dabigatran, a drug that is more potent than warfarin and causes less cerebral bleeding," said lead author Hans-Christoph Diener, M.D., Ph.D., professor and chairman of neurology at University Hospital in Essen, Germany.

In the overall RELY study population the higher dose of dabigatran was also linked with higher rates of gastrointestinal bleeding, but Diener said that was of less concern. "Generally gastrointestinal bleedings can be handled, but severe intracranial bleeding with warfarin usually leads to death or permanent disability," he noted.

Warfarin has long been the recommended drug for preventing strokes in people with atrial fibrillation.  However, warfarin increases the risk of brain and gastrointestinal bleeding, and the drug is difficult to manage, Diener said.  It adversely interacts with some foods and drugs, and its therapeutic range is narrow.  Too much warfarin can cause bleeding, including in the brain, and too little can result in an ischemic stroke – caused by blood clots dislocated from the heart.  Thus, physicians must monitor patients closely.

"Dabigatran's efficacy is independent of body weight and age, there are no food interactions, and you don't have to see a physician regularly to monitor the coagulation system," he said.

The risk of stroke is increased in atrial fibrillation patients, and especially in those who have already suffered a stroke or transient ischemic attack.