RE-LY study: New oral blood thinner better and safer

Dabigatran, a novel oral direct thrombin inhibitor, is not only more effective than warfarin, but also safer in preventing stroke in patients with atrial fibrillation (AF), finds the highly-anticipated RE-LY* trial.

Dabigatran 150 mg twice daily significantly reduced the risk of stroke by 34 percent compared to warfarin (P<0.001), while a lower dose of 110 mg twice daily showed similar efficacy to warfarin, but with considerably less major bleeding, reducing major bleeding rates by 20 percent (P=0.003).

“This is the first time in more than 50 years that a new oral blood thinner has been developed which has been found to be safer and more effective than existing therapy,” said Professor Stuart Connolly, co-principal investigator of RE-LY.

If the RE-LY results are translated into clinical practice, dabigatran 150 mg could prevent approximately 3,000 more strokes per day, worldwide, compared to well-controlled warfarin, according to materials distributed at a press conference held during the recent European Society of Cardiology Congress, in Barcelona, Spain.

“The results of dabigatran in RE-LY exceeded all our expectations. We now have an oral treatment which offers superior protection from stroke with less bleeding and without the need for routine monitoring,” said Connolly, who is director, division of cardiology at The Population Health Research Institute, McMaster University, Hamilton, Canada.

“In addition to protecting patients from strokes, we as physicians are especially concerned about life-threatening or disabling bleeding with warfarin due to its narrow therapeutic window. On top of the efficacy, dabigatran has shown equally impressive safety results, offering a wider safety margin.”

The landmark study is the largest AF outcomes trial ever conducted.

Originally designed as a non-inferiority trial against warfarin, two doses of dabigatran (150 mg twice daily and 110 mg twice daily) were compared with well-controlled warfarin in an open label, randomized trial of 18,113 AF patients in 44 countries. Average treatment duration was 2 years with at least 1 year of follow-up. [N Engl J Med 2009; Epub ahead of print]

Dabigatran performed impressively in key secondary endpoints of hemorrhagic stroke and vascular mortality.

“What’s truly remarkable about the RE-LY study is that in addition to reducing strokes due to blood clots, this treatment has also reduced strokes due to bleeding into the brain – one of the most feared consequences of antithrombotic therapy,” said Connolly.

“Both doses have shown a lower rate of hemorrhagic stroke than warfarin … the risk reductions are remarkable with relative risks of 0.31 and 0.26, indicating 69 percent and 74 percent relative risk reductions for this outcome. Both results are highly statistically significant.”

Each dose offers advantages over warfarin, said Connolly. The 150 mg dose is more effective, but dabigatran 110 mg has the better safety profile. Further trials are needed to determine which dose can be recommended for which patients, but as both offer benefits to patients, there is the potential for physicians to tailor therapy to individual patient characteristics, said Connolly.

Both doses significantly reduced intra-cranial, life-threatening and total bleeding. In terms of safety, dabigatran had no liver, or other major toxicity. Increased dyspepsia compared with warfarin and GI bleeding were reported, however.

A slight increase in the rate of myocardial infarction compared with warfarin treatment (0.7 percent for both dabigatran doses versus 0.5 percent for warfarin) was observed.

“This was an unexpected finding and still requires us to understand it better,” said Connolly. “The working hypothesis now is that we know that warfarin is effective in reducing myocardial infarction and it may well be that warfarin is more potent at this particular aspect of antithrombotic therapy than is dabigatran.”

Warfarin has been the gold standard for stroke-reducing therapy in AF for 20 years, and, when used correctly, can produce highly effective results. In real-life clinical practice, however, warfarin comes with a number of limitations for both patients and doctors. Its narrow therapeutic window and the large number of food and drug interactions make maintaining the therapeutic dose a constant struggle, requiring regular blood testing and dose adjustments.

Dagibatran is currently approved for the primary prevention of venous thromboembolic events in adults who have undergone elective total hip or elective total knee replacement surgery.

*RE-LY: Randomized Evaluation of Long-term Anticoagulant Therapy

Source: Medical Tribune