For a-fib, a welcome alternative to warfarin

Douglas Dawley, M.D.Douglas Dawley, M.D.
Cardiologist, Providence Heart and Vascular Institute

Published February 2011

The U.S. Food and Drug Administration’s recent approval of dabigatran – the first oral antithrombin to enter the market – presents a favorable alternative to warfarin in patients with nonvalvular atrial fibrillation.

Patients and physicians alike have lived with the frustrations of warfarin for more than 50 years. Warfarin has a narrow therapeutic window and requires frequent blood-test monitoring and dose adjustments due to its varying therapeutic effects and drug-food interactions. Xemilogatran, the first oral antithrombin inhibitor to be tested, failed to gain FDA approval in 2006 because of liver toxicity.

Dabigatran, brand name Pradaxa, does not require blood-test monitoring. It was approved based on the RE-LY trial, in which it was found to reduce stroke or systemic embolization by 35 percent compared to warfarin.

Pradaxa also lowered the rate of ischemic, hemorrhagic and disabling strokes compared to warfarin. These benefits did not occur at the expense of increased bleeding. In fact, overall bleeding rates were 9 percent lower with Pradaxa, and included significantly less intracranial hemorrhage and life-threatening bleeds. Rates of GI bleeding and GERD symptoms, however, were slightly higher with Pradaxa.

A few caveats do exist with Pradaxa. It is contraindicated in patients on rifampin. Since Pradaxa is renally metabolized, the dose in patients with Creat Cl 15-30 ml/min must be reduced to 75 mg bid. It probably should not be used if Creat Cl is less than 15 ml/min and if the patient is on dialysis.

Providence Clinical Pharmacy Services has worked with anticoagulation clinics to identify patients who might be good candidates for Pradaxa. They include those who have difficult-to-manage INRs or who can’t travel to clinics. These are often elderly patients, a population well represented in the RE-LY trial and one that saw significant clinical benefit from dabigatran. The elderly have the highest risk for stroke, yet they are often undertreated with warfarin. Dabigatran represents a good alternative for this population.

A RE-LY substudy recently published in Circulation found that frequencies of stroke and major bleeding within 30 days of cardioversion were low on the two doses of dabigatran and comparable to those on warfarin with or without transesophageal echocardiographic guidance. Thus, dabigatran is a reasonable alternative to warfarin in patients requiring cardioversion.

Oral anticoagulation choices for a-fib will no doubt increase in the near future. For example, an anti-Xa drug, rivaroxaban, was found to be non-inferior to warfarin in high-risk a-fib patients, according to results of the ROCKET AF study presented at a recent American Heart Association meeting. Whether rivaroxaban will be approved by the FDA is unclear, yet other anti-thrombin and anti-Xa drugs are also in clinical trials.

Clinical articles by Douglas Dawley, M.D.