A new oral drug that does not need monitoring showed benefits over warfarining patients with atrial fibrillation in the phase 3 RE-LY (Randomised Evaluation of Long-Term Anticoagulation Therapy) trial, suggesting that a viable replacement for warfarin has finally been found.

In the trial, dabigatran (Pradaxa) given at a dose of 110 mg was associated with similar rates of stroke and systemic embolism to warfarin but with less major bleeding. A higher dose of dabigatran (150 mg) produced lower rates of stroke and systemic embolism than warfarin with similar rates of major bleeding.

Dabigatran, a thrombin inhibitor, is one of several new oral anticoagulants being developed. It has recently been made available in Europe for the prevention of venous thromboembolism during hip- and knee-replacement surgery.

The RE-LY study is the largest outcomes study in atrial fibrillation ever conducted. It was carried out in 44 countries and randomised 18,113 patients with atrial fibrillation and at least one other risk factor for stroke to receive dabigatran at either 110 mg or 150 mg twice daily or warfarin adjusted to an INR of 2.0 to 3.0. Aspirin was taken throughout the trial by about 20% of patients. The median duration of the follow-up period was two years. The primary end point was stroke or systemic embolism.

Results (table 1) showed that the higher dose of dabigatran significantly reduced the risk of stroke by 34% compared to warfarin (p<0.001), with a similar bleeding risk. The lower dose had a similar effect to warfarin in the prevention of stroke, but with significantly less major bleeding. The risk of myocardial infarction was increased with dabigatran, which just reached significance in the high-dose group. Both dabigatran groups showed significantly lower rates of haemorrhagic strokes compared with warfarin.

Dabigatran seems not to be merely a superior therapy, but will hopefully be a stimulus to a paradigm change in the antithrombotic management of atrial fibrillation. But some caution has been voiced over the need for longer-term safety follow-up, given the bad experience seen with the last warfarin replacement candidate, ximelegatran, which had to be removed from the market shortly after launch because of liver toxicity. No signs of liver toxicity were seen in the RE-LY trial, the main side-effect of dabigatran being dyspepsia.

The RE-LY results were published online in the New England Journal of Medicine (10.1056/NEJMoa0905561) to correspond with their release in Barcelona.