The Medical Letter on Drugs and Therapeutics
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1492
Which Oral Anticoagulant for Atrial Fibrillation?
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 Select a term to see related articles  andexanet alfa   Anticoagulants   apixaban   Atrial fibrillation   Coumadin   Dabigatran   edoxaban   Eliquis   fresh frozen plasma   idarucizumab Praxbind   noac   Pradaxa   prothrombin complex concentrates   Rivaroxaban   Savaysa   Vitamin K   Warfarin   Xarelto 

Direct-to-consumer advertisements continue to urge patients who take warfarin (Coumadin, and others) for atrial fibrillation to ask their doctors about the benefits of one or another of the newer oral anticoagulants.

WARFARIN — In patients with nonvalvular atrial fibrillation, warfarin reduces the risk of thromboembolic stroke by about 60%.1 If necessary, vitamin K, prothrombin complex concentrate, or fresh frozen plasma can reverse its anticoagulant effect.2 Drawbacks of warfarin include unpredictability and variability in dosage requirements, dietary restrictions, interactions with many other drugs, and the need for close monitoring to keep the international normalized ratio (INR) in the therapeutic range (2-3).

DIRECT ORAL ANTICOAGULANTS — The direct thrombin inhibitor dabigatran etexilate (Pradaxa) and the direct factor Xa inhibitors apixaban (Eliquis), edoxaban (Savaysa), and rivaroxaban (Xarelto) do not require routine monitoring of coagulation times and they have fewer drug interactions than warfarin.

Drawbacks of the direct oral anticoagulants include absence of any method for monitoring the extent of their anticoagulant effect, short half-lives that increase the risk of thrombosis with missed doses, lack of data on their use in patients with end-stage renal disease, and higher drug costs.

Efficacy – In the pivotal clinical trials against warfarin that led to their approval by the FDA, all of the direct oral anticoagulants were at least noninferior to warfarin for prevention of stroke or systemic embolism in patients with atrial fibrillation. In patients taking warfarin, the INR was in the therapeutic range only 55-65% of the time.3-6 Edoxaban was less effective than warfarin for prevention of stroke or systemic embolism in patients with a CrCl >95 mL/min; it was more effective in those with a CrCl between 50 and 80 mL/min.7

Bleeding – All of the direct oral anticoagulants had significantly lower rates of intracranial bleeding and hemorrhagic stroke than warfarin in the pivotal clinical trials. Compared to warfarin, the rates of major bleeding with dabigatran and rivaroxaban were similar and the rates with apixaban and edoxaban were significantly lower.

Reversibility – In 2015, the FDA approved idarucizumab (Praxbind) for urgent reversal of the anticoagulant effect of dabigatran.8 No specific antidote is available in the US for the three direct factor Xa inhibitors, but in one study in healthy volunteers, an investigational synthetic product (andexanet alfa) reversed the anticoagulant effects of apixaban and rivaroxaban within minutes.9 The results of some studies suggest that the anticoagulant effects of all of the direct oral anticoagulants may be reversed by prothrombin complex concentrate.10

CONCLUSION — The direct oral anticoagulants dabigatran (Pradaxa), apixaban (Eliquis), edoxaban (Savaysa), and rivaroxaban (Xarelto) have been at least as effective as warfarin (Coumadin, and others) in preventing stroke or systemic embolism in patients with nonvalvular atrial fibrillation, and they appear to be safer. Patients well controlled on warfarin (INR stable in the therapeutic range) could stay on it. For all others, one of the direct oral anticoagulants might be a better choice. Head-to-head comparisons of the new drugs are lacking.

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