Conference Coverage
Anticoagulant edoxaban comparable with warfarin in atrial fib
Major finding: The annualized rate of stroke or embolic events was 1.50% with warfarin vs.
A detailed transition plan protected most atrial fibrillation patients from strokes and major bleeding when they switched oral anticoagulants, researchers reported in the August issue of the Journal of the American College of Cardiology.
Following such a plan could help patients safely switch anticoagulants in clinical practice, said Dr. Christian Ruff at Harvard Medical School in Boston and his associates.
They reported an analysis from the ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) trial, which randomized more than 21,000 AF patients at high risk of stroke to either the investigational factor Xa inhibitor edoxaban or warfarin. Edoxaban was shown noninferior to warfarin in preventing stroke or systemic embolism (N. Engl. J. Med. 2013; 369:2093-104).
In the past, researchers from the ROCKET AF and ARISTOTLE trials reported excess strokes and bleeding events after patients were switched from blinded factor Xa inhibitors to open-label antithrombotics, the investigators said.
In response, ENGAGE AF-TIMI 48 patients and their physicians decided together whether to switch to an open-label vitamin K antagonist (VKA) or a newer oral anticoagulant at the end of the trial, the researchers said. Patients then received a transition kit with a 14-day supply of either a half-dose edoxaban for patients switching from blinded edoxaban to open warfarin, or a placebo for patients switching from blinded to open warfarin. Patients also underwent at least three international normalized ratio (INR) tests during the first 2 weeks of the transition period and were dosed based on a VKA titration algorithm designed to quickly reach therapeutic INR, they said.
Among 13,642 ENGAGE AF-TIMI patients alive at the end of the trial, 68.2% transitioned to a VKA and 31.2% to a new oral anticoagulant, said the researchers.
Thirty days later, rates of therapeutic INR, stroke, and bleeding events were similar regardless of whether patients had taken low-dose edoxaban, high-dose edoxaban, or warfarin during the trial, they reported. In all, 98.7% of patients switched from high-dose edoxaban had at least one INR of 2 or more, compared with 98.9% of patients switched from low-dose edoxaban and 99.4% of patients switched from warfarin, they said (J. Am. Coll. Cardiol. 2014;64:576-84).
Post-transition rates of strokes (1.85% to 1.90% per year) and major bleeding (2.69% to 4.76% per year) also were similar among the three trial groups, they added.
The excess ischemic events in earlier trials probably resulted from relative delays in achieving a therapeutic INR when patients were switched from a newer oral anticoagulant to an open-label VKA, the researchers noted, adding that "VKAs are effective as long as a therapeutic INR can be rapidly reached and maintained."
Daiichi Sankyo funded the ENGAGE AF-TIMI trial. Dr. Ruff reported having been a consultant and receiving honoraria from Daiichi Sankyo. Two coauthors reported financial relationships, six reported having received grant support, and two reported employment with Daiichi Sankyo.