New guidelines for managing patients with nonvalvular atrial fibrillation recommend dabigatran, rivaroxaban, and apixaban, as well as warfarin, and call on physicians to use a more comprehensive stroke risk calculator.
"I think physicians are still learning how to use the newer anticoagulants, and this is something that will require time," said Dr. Craig T. January, chair of the AF guidelines committee, assembled by the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society.
The guidelines, published in Circulation and in the Journal of the American College of Cardiology, focus on nonvalvular AF and feature a detailed dosing chart organized by anticoagulant type and renal function, which is impaired in up to 20% of those with AF.
"The goal was to create a straightforward chart on how to use these drugs," said Dr. January, a clinician/scientist with the University of Wisconsin School of Medicine and Public Health, Madison.
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Dabigatran, rivaroxaban, and apixaban, as well as warfarin, are recommended for managing patients with nonvalvular atrial fibrillation.
Dabigatran (Pradaxa) and rivaroxaban (Xarelto) are not recommended for AF patients with nonvalvular disease and end-stage kidney disease, either on or off dialysis, because of a lack of evidence from clinical trials regarding the balance of risks and benefits.
No recommendation was made for apixaban (Eliquis) in patients with severe or end-stage renal impairment, because of a lack of published data, although a recent secondary analysis of the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial suggests the direct factor Xa inhibitor provides the greatest reduction in major bleeding in patients with impaired renal function compared with warfarin (Eur. Heart J. 2012;33:2821-30).
The guidelines advise clinicians to evaluate renal function prior to initiating any of the direct thrombin or factor Xa inhibitors, and to reevaluate at least annually and when clinically indicated.
Previously, warfarin (Coumadin) was the only recommended anticoagulant in the 2006 guidelines. It’s admittedly cheaper, but the guidelines note that the novel anticoagulants eliminate dietary limitations and the need for repeated international normalized ratio (INR) monitoring, and have more predictable pharmacological profiles and fewer drug-drug interactions.
The oral agents have revolutionized the treatment of AF since entering the market in the past few years, but by no means replace warfarin.
For patients with nonvalvular AF who are well controlled and satisfied with warfarin therapy, the guidelines say, "It is not necessary to change to one of the newer agents," Dr. January observed.
Warfarin should also be used for valvular AF to manage patients with a mechanical heart valve or hemodynamically significant mitral stenosis because these populations were excluded from all three major trials – RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy With Dabigatran Etexilate), ROCKET-AF (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation), and ARISTOTLE – that led to the approval of the newer anticoagulants.
Dabigatran is specifically not recommended for patients with a mechanical valve because of the potential for harm, which was recently recognized by the Food and Drug Administration.
The document includes a section on dose interruption and bridging therapy, which in part reflects the fact that the new oral agents carry a black box warning from the FDA because discontinuation can increase the risk of thromboembolism. In addition, reversal agents are in development, but they are not currently available should immediate reversal be needed.
The new recommendations will elicit discussion, but are not expected to be controversial like the updated cholesterol management guidelines recently released by the American College of Cardiology and the American Heart Association, Dr. January said.
Another noteworthy change is the diminished use of aspirin in preventing stroke. "Most of the published data have shown that aspirin is not as effective as full anticoagulation and that aspirin itself in many trials has little benefit. This was a point of a lot of discussion in the committee," he said.
To calculate stroke risk, the guidelines recommend that clinicians use the CHA2DS2-VASc (Congestive heart failure, Hypertension, Age 75 or older (doubled), Diabetes mellitus, Prior Stroke or TIA or thromboembolism (doubled), Vascular disease, Age 65 to 74 years, Sex category female) calculator because it has a broader score range (0 to 9) and includes a larger number of risk factors than the older CHADS2 score.
"What the CHA2DS2-VASc provides is better discrimination for patients at the lower end of risk," Dr. January said. "I think there was uniform agreement in the committee that the CHA2DS2-VASc was the preferred risk calculator and that we should move on from the CHADS2 score.