The recently approved anticoagulant dabigatran (Pradaxa) has been recommended as an alternative to warfarin for stroke prevention with atrial fibrillation, according to a “focused” update of guidelines from the American Heart Association, American College of Cardiology, and the Heart Rhythm Society.The guideline update focuses specifically on dabigatran because, with its approval in October
, it is the first new oral anti-clotting drug on the market in more than 50 years, the authors of the update wrote.
The new recommendation was published online in Circulation: Journal of the American Heart Association, the Journal of the American College of Cardiology, andHeartRhythm.
- Dabigatran, an oral direct thrombin inhibitor, is recommended by the American Heart Association and other professional groups as a useful alternative to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation.
- This is a Class I, Level B recommendation, which indicates support from a single randomized trial.
- This guideline does not apply to patients with a prosthetic heart valve, hemodynamically significant valve disease, or severe renal failure.
Studies have shown that about 40% of patients with afib who should be taking an oral anticoagulant are not being treated. Ralph Sacco, MD, a neurologist at the University of Miami and president of the AHA, said he hopes having another option will reduce that number.
“What we’re hoping is that more physicians will practice with the guidelines and get [patients] on oral anticoagulants — warfarin, or now, the new anticoagulant, dabigatran — and then we will hopefully reduce the number of patients with atrial fibrillation who go on to stroke,” he said.
In a Class I, Level B recommendation — indicating support from a single randomized trial — the organizations advised that dabigatran is useful as an alternative to warfarin for preventing stroke and systemic thromboembolism in patients with paroxysmal to permanent afib and risk factors for stroke or systemic embolization.
The guidance applies to patients who do not have a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure, or advanced liver disease.
Dabigatran’s approval and inclusion in the guidelines were based on the results of the 18,000-patient (Randomized Evaluation of Long-Term Anticoagulation Therapy) RE-LY trial, which compared the direct thrombin inhibitor with warfarin in patients with afib who had at least one additional risk factor for stroke.
The RE-LY trial showed that the twice-daily 150-mg dose of dabigatran was superior to warfarin and that the 110-mg dose was noninferior to warfarin for preventing stroke and systemic embolism.
In the trial, warfarin was associated with a major bleeding rate of 3.57% per year, which was comparable to the rate with the higher dose of dabigatran (3.32%, P=0.32) and significantly higher than that with the lower dose (2.87%, P=0.003).
There was no mortality difference between the two drugs.
Based on the results, the FDA approved two doses of dabigatran — the 150-mg dose for patients with a creatinine clearance of greater than 30 mL/min and a 75-mg dose, which was not evaluated in the trial, and for patients with a creatinine clearance of 15 to 30 mL/min.
Dabigatran therapy does not require the continual INR testing that accompanies warfarin therapy and is less likely to have interactions with foods or other drugs. However, the authors of the update noted that because of its twice-daily dosing and greater risk of nonbleeding side effects — including dyspepsia — there may be little to gain from switching patients who have good INR control with warfarin to the new drug.
Sacco agreed, telling MedPage Today that “the longer somebody is on oral anticoagulants with warfarin and doing well, I don’t necessarily feel strongly that one needs to switch.”
For a new patient, Sacco said, the choice between dabigatran and warfarin will come down to several factors, including the need for INR monitoring with warfarin, the decreased likelihood of food interactions with dabigatran, the patient’s history of bleeding complications with oral anticoagulants, and patient preference.
He said cost was one potential downside of the newer drug, which is more expensive than warfarin.
Larry Goldstein, MD, director of the stroke center at Duke University, also acknowledged the higher cost but said the comparison was more complex than looking just at the expense of buying a new drug.
The cost of the blood tests needed to monitor INR with warfarin, as well as the cost of treating any excess strokes with one agent over another, would also have to be considered, he said.
Goldstein also added that dabigatran is not free from all drug interactions either — noting that the antibiotic, rifampin, can reduce its anti-clotting effects while the antiarrhythmic agent, amiodarone, and the antihypertensive drug, verapamil, can enhance its anticoagulation effects.
Another potential drawback, he said, is the uncertainty about the safety of using systemic thrombolysis on patients taking dabigatran who have an acute stroke.
Wann reported that he had no conflicts of interest. The other members of the writing committee reported relationships with AfibProfessional.org, Boehringer Ingelheim, Medtronic, ARYx Therapeutics, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, and Portola Pharmaceuticals.
The reviewers reported relationships with Medtronic, ARYx Pharmaceuticals, Boehringer Ingelheim, Daiichi Sankyo, Portola Pharmaceuticals, AstraZeneca, and Bristol-Myers Squibb.