NEW YORK (Reuters Health) – A “focused update” to existing guidelines on the management of patients with atrial fibrillation (AF) states that the recently approved oral direct thrombin inhibitor dabigatran (Pradaxa, Boehringer Ingelheim) is a useful alternative to warfarin (Coumadin, Bristol-Myers Squibb) for stroke risk reduction in patients with nonvalvular AF.
The focused update – a collaborative effort by the American College of Cardiology (ACC), the American Heart Association (AHA) and the Heart Rhythm Society (HRS) – was published online this week simultaneously in Circulation: Journal of the American Heart Association, Journal of the American College of Cardiology, and Heart Rhythm.
It specifically addresses dabigatran, the first new oral anticoagulant to become available for clinical use in more than 50 years.
The update says dabigatran is “useful as an alternative to warfarin for the prevention of stroke and systemic thromboembolism in patients with paroxysmal to permanent AF and risk factors for stroke or systemic embolization who do not have a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure (creatinine clearance < 15 mL/min), or advanced liver disease (impaired baseline clotting function).”
It’s a Class I, Level B recommendation, the authors of the update note. Dr. L. Samuel Wann, of the Wisconsin Heart Hospital in Wauwatosa, chaired the writing committee.
US FDA approval of dabigatran on October 19, 2010, was based on findings from the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy), which compared dabigatran (110 mg and 150 mg twice daily) with warfarin in more than 18,000 patients with AF and at least one other risk factor for stroke.
The trial showed that for stroke prevention, the higher dose of dabigatran was superior to warfarin and the lower dose was noninferior to warfarin. Rates of major bleeding were comparable with the higher dose of dabigatran and warfarin (3.32% and 3.57% per year, respectively) and lower with the lower dabigatran dose (2.87% per year). There was no difference in mortality with dabigatran compared with warfarin.
The FDA approved the 150-mg twice daily dose for patients with a creatinine clearance > 30 mL/min and a 75-mg twice daily dose for patients with severe renal impairment (creatinine clearance 15 to 30 mL/min). There are no dosing recommendations at a creatinine clearance < 15 mL/min. The FDA did not approve the 110-mg twice daily dose studied in RE-LY.
Dabigatran or Warfarin?
The committee notes in their report that because of the twice-daily dosing and a greater risk of nonhemorrhagic side effects with dabigatran, “patients already taking warfarin with excellent INR [international normalized ratio] control may have little to gain by switching to dabigatran.”
In the RE-LY trial, dyspepsia occurred more frequently with dabigatran (11.8% and 11.3% for the higher and lower dose, respectively) compared to warfarin (5.8%). Rates of myocardial infarction were also higher with dabigatran (0.82% and 0.81% for the two doses, respectively) than with warfarin (0.64%).
“However, the increase in myocardial infarction seen in RE-LY was not statistically significant in the dabigatran groups,” the authors note. Drug discontinuation rates were slightly higher in the dabigatran arms than the wafarin arm.
When thinking about patients with AF and at least 1 additional risk factor for stroke who could benefit from treatment with dabigatran as opposed to warfarin, the committee advises clinicians to “consider individual clinical features, including the ability to comply with twice-daily dosing, availability of an anticoagulation management program to sustain routine monitoring of INR, patient preferences, cost, and other factors.”
To see the update, visit the AHA’s website www.my.americanheart.org), the ACC’s website www.cardiosource.org and the Heart Rhythm Society’s website www.hrsonline.org. The document contains a complete list of relevant disclosures for all members of the committee that participated in the focused updated on dabigatran.