The popularity of the next generation of anticoagulation therapies could be dependent on whether reversing agents for the newest drugs can be developed, says a hospitalist who heads an antithrombotic clinic.
In October, the FDA approved dabigatran etexilate (Pradaxa) for atrial fibrillation (AF) patients. In a noninferiority study published last month, investigators found that treatment with oral rivaroxaban alone (15mg twice daily for three weeks, followed by 20mg once daily) showed effectiveness versus subcutaneous enoxaparin followed by a vitamin K antagonist. In relation to the primary outcome of recurrent DVT, rivaroxaban had noninferior efficacy (36 events [2.1%], vs. 51 events, 0.44 to 1.04; P<0.001) (N Engl J Med. 2010;363:2499-2510).
Another study, dubbed ROCKET-AF (PDF) and unveiled at an American Heart Association meeting in November, reported that rivaroxaban was noninferior to warfarin in the treatment of stroke and non-CNS embolism. Study patients treated with rivaroxaban exhibited significantly less events (1.71) per 100 patient-years (188 patients) compared with those on warfarin (2.16; 241 patients; P<0.001 for noninferiority, P=0.018 for superiority).
A third medication, apixaban, which also acts as a direct
fact Xa inhibitor, is currently being tested in clinical trials.
Geno Merli, MD, senior vice president and chief medical officer at Thomas Jefferson University Hospital and head of the Jefferson Antithrombotic Therapy Service, both in Philadelphia, says one of the most pressing issues with the Xa inhibitors is that there is not yet a reversing agent for the drugs should complications arise. “I can reverse Coumadin,” Dr. Merli says. “I can give vitamin K or fresh frozen plasma. You’re giving back the factors that were affected.”
Dr. Merli adds that pharmaceutical companies already are working on development of reversing agents and antibodies, but until those are approved, some physicians might shy away from new anticoagulant therapies. Still, he encourages physicians to get the medications added to their respective hospitals’ medicine cabinets as quickly as feasible.
“You’ve got to have it on your formulary because you have to know the drug,” Dr. Merli says. “You have to have it for the doctor who will choose to use it or the patient who comes in already on it.”