What is the efficacy and safety of edoxaban (Savaysa) use in patients with atrial fibrillation (Afib) (AF)?

Updated: Nov 18, 2019
  • Author: Lawrence Rosenthal, MD, PhD, FACC, FHRS; Chief Editor: Jeffrey N Rottman, MD  more...
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Answer

Edoxaban (Savaysa) was approved for the prevention of thromboembolism in AF by the FDA in January 2015 on the basis of results from the ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction Study 48) trial. [87] This double-blind, noninferiority trial randomized 21,105 patients with nonvalvular AF to high-dose edoxaban (60 mg daily), low-dose edoxaban (30 mg daily), or warfarin (creatinine clearance up to 30 mL/min was an exclusion criterion). Mean CHADS2 score for the subjects in this trial was 2.8. In intention-to-treat analyses, both doses of edoxaban were noninferior to warfarin for prevention of the stroke and systemic embolic events; however, there was a trend toward superiority for high-dose edoxaban (embolic risk of 1.57% with high-dose edoxaban compared to 1.8% with warfarin; P = 0.08). [87]

Of note, in participants with a creatinine clearance of 95 mL/min or greater, the hazard ratios (HRs) for developing embolic events were similar between the high-dose edoxaban and the warfarin groups. [87] Consequently, the FDA recommends avoiding edoxaban in patients with a creatinine clearance of 95 mL/min. [88] Both doses of edoxaban were reported to be superior to warfarin for all types of bleeding, except gastrointestinal bleeding wherein low-dose edoxaban was superior (HR: 0.67 (ie, 33% lower risk of bleeding); P< 0.001), whereas high-dose edoxaban was inferior to warfarin (HR: 1.23 [ie, 23% higher risk of bleeding]; P = 0.03).

A meta-analysis of four randomized trials involving 42,411 patients who received newer anticoagulants and 29,272 who received warfarin showed that, in patients with AF, the newer oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban protected against stroke or systemic embolism better than warfarin and had comparable safety profiles. [87, 89, 90, 91]

The newer anticoagulants also significantly reduced the incidence of all-cause mortality and intracranial hemorrhage, but increased gastrointestinal bleeding. Median follow-up periods ranged from 1.8 years to 2.8 years. The risk of stroke or systemic embolic events was reduced by 19% with the newer anticoagulants compared with warfarin; hemorrhagic strokes accounted for a large proportion of the reduction. Compared with warfarin, low-dose new anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events and a more favorable bleeding profile, but significantly more ischemic strokes. [87, 89, 90, 91]


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