eCardioVascular Beat

Dabigatran offers more benefits, fewer complications than warfarin

Doug Dawley, M.D.

Cardiologist, Providence Portland Medical Center
The Oregon Clinic

The recent FDA approval of dabigatran (Pradaxa) – the first oral anti-thrombin 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 (INR 2-3) and requires frequent blood-test monitoring as well as dose “Pradaxa also lowered the rate of ischemic stroke, hemorrhagic stroke and disabling strokes compared to warfarin.” adjustments due to its varying therapeutic effects and drug-food interactions. Xemilogatran, the first oral anti-thrombin inhibitor to be tested, failed to gain FDA approval in 2006 because of liver toxicity.

Dabigatran does not require blood-test monitoring and was approved based on its stellar performance in the RE-LY trial (NEJM 2009; 361: 2342-2362). In that study, 18,113 patients with nonvalvular afib and other risk factors for stroke underwent unblinded randomization to warfarin (INR 2-3), Pradaxa 120 mg BID or Pradaxa 150 mg BID.

At two years the primary endpoint of stroke or systemic embolization was reduced by 35 percent with Pradaxa 150 mg BID compared to warfarin (2.2 percent versus 3.4 percent p=.0001).

Pradaxa also lowered the rate of ischemic stroke, hemorrhagic stroke 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. However, rates of GI bleeding and GERD symptoms 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, and should probably not be used if Creat Cl is less than 15 ml/min and if the patient is on dialysis.

Steve Stoner, regional director of Providence Clinical Pharmacy Services, has worked with anticoagulation clinics to identify patients who might be good candidates for Pradaxa. They include those with difficult-to-manage INRs or those who can’t travel to the clinics. Often these are 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 substudy of RE-LY, recently published in Circulation (2011; 123:131-136), looked at 1983 cardioversions in RE-LY. The frequencies of stroke and major bleeding within 30 days of cardioversion on the two doses of dabigatran were low 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 afib, no doubt, will increase in the near future. For example, an anti-Xa drug, rivaroxaban, was found to be non-inferior to warfarin in high-risk afib patients, according to results of the ROCKET AF study recently presented at the American Heart Association. Whether rivaroxaban will be approved by the FDA is unclear, yet other anti-thrombin and anti-Xa drugs are also in clinical trials.

Other articles by Douglas Dawley, M.D.

• Reducing radiation exposure from cardiac testing
• Case study: When genes predict CAD