A Good Alternative to Warfarin in Managing A-Fib

It’s taken a little time, but patients with atrial fibrillation (A-Fib) now have a drug that’s considered better than warfarin to help prevent them having an ischemic stroke.  In August 2009 the New England Journal of Medicine published the results of the RE-LY trial: the Randomized Evaluation of Long-Term Anticoagulant Therapy trial.  The results showed that dabigatran (at that time marketed as Pradaxa® outside the USA) was more effective than warfarin at stopping both ischemic (blood-clot) strokes and bleeding (hemorrhagic) strokes.

The RE-LY study was done at 951 centers in 44 countries, and involved over 18,000 A-Fib patients who had at least one other risk factor for stroke.  Two doses of dabigatran (150 mg and 110 mg), each given twice daily, were compared with warfarin given in an adjusted dose regime. 

Compared with warfarin, the 150 mg dose of dabigatran reduced ischemic plus hemorrhagic strokes by 34% (the rates were 1.69% for warfarin vs. 1.11% for 150 mg dabigatran; there was no significant difference in the rate of bleeding.  At the 110 mg dose, dabigatran had a 20% lower rate of bleeding than warfarin: 2.71% vs. 3.36%; but the risk of stroke was only 9% lower, though still statistically significant.        

The authors of the study concluded that they had shown that, in patients with atrial fibrillation, 110 mg doses of dabigatran were associated with rates of stroke that were similar to warfarin, but with a lower rate of major hemorrhage. At higher doses (150 mg), dabigatran produced lower rates of stroke, but similar rates of major hemorrhage.  Clearly, from both efficacy and safety viewpoints, treatment with dabigatran was clinically superior.

Another large dabigatran study (2500 patients) done in 2009 showed the drug to be ‘non-inferior’ to warfarin in the treatment of acute venous thrombosis.  There was a similar rate of major bleeding and a lower rate of combined major plus minor bleeding with dabigatran compared to warfarin.

 The superiority of dabigatran is not confined to clinical safety and effectiveness.  Warfarin is difficult and time-consuming to manage, requiring frequent blood tests of anticoagulant effectiveness, and carries the risk of food and drug interactions. Dabigatran does not require laboratory monitoring.

Based largely on the RE-LY trial, as well as reports for overseas, the FDA approved Pradaxa® (dabigatran) at the 150 mg dose level for use in A-Fib in October 2010.  And now, in 2011, we are seeing the ads for the drug on TV screens everywhere.  If the real-life results hold up well, confirming the findings from the major trials, warfarin clinics may well become a thing of the past.  The extra costs of the new drug will hopefully be covered by these shrinking warfarin-clinic costs.  The dabigatran story is the way that new drug development is supposed to work (though the time-to-market could, with advantage, be reduced.)