Chicago, IL—The new oral anticoagulants— the factor Xa inhibitors rivaroxaban (Xarelto) and apixaban (Eliquis), and the direct thrombin inhibitor dabigatran (Pradaxa)—are superior to warfarin (Coumadin) in preventing stroke and systemic embolism in patients with atrial fibrillation (AF), according to a review/meta-analysis conducted by Mark J. Eisenberg, MD, MPH, Associate Professor of Medicine, Director of McGill Cardiology Fellowship Programs at McGill University, Montreal, Quebec, Canada, and colleagues at the 2012 American College of Cardiology meeting.
These newer agents have been shown to be superior to warfarin on efficacy end points and to reduce the risk for a major bleeding event compared with warfarin, although they do appear to increase the risk for gastrointestinal (GI) bleeding.
Superior Efficacy in Stroke Prevention
This review encompassed the 3 large, randomized controlled trials Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY); Apixaban for the Prevention of Stroke in Subjects with Atrial Fibrillation (ARISTOTLE); and 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 (ROCKET-AF).
Dr Eisenberg’s group used a random effects model to pool the efficacy and safety data across the 3 trials, in which more than 40,000 patients were randomized to one of these new oral anticoagulants or to warfarin.
Patients randomized to one of the new oral anticoagulants had a 22% decreased risk for a composite end point of all stroke and systemic embolism compared with patients randomized to warfarin.
In this analysis, compared with warfarin, the new oral anticoagulants were associated with a:
- 23% reduction in the relative risk for ischemic and unidentified stroke
- 55% risk reduction of hemorrhagic stroke
- 12% risk reduction of all-cause mortality
- 13% risk reduction of vascular mortality.
The risk for myocardial infarction was similar between warfarin and the new anticoagulants.
Reduced Risk for Major Bleeding, but Increase for GI Bleeding
In addition, the relative risk for major bleeding was 12% lower with the new anticoagulants compared with warfarin, but the relative risk for GI bleeding was increased by >25% with the newer agents.
“These new oral anticoagulants are easily administered and do not require monitoring, making them promising alternatives for prevention of stroke and systemic embolism in patients with AF,” Dr Eisenberg stated.
Corey Miller, a medical student at McGill University and a coinvestigator in this analysis, said that the results suggest notable trends with the new anticoagulants. More research will be required to confirm the suggestion for decreased risk for major bleeding and increased GI bleeding with the new agents. Although cost was not included in this meta-analysis, he noted that the extra cost for the new medications may be offset by the significant cost associated with monitoring patients receiving warfarin.
These same 3 trials, along with the PETRO (Stroke Prevention in Patients with AF by Treatment with Dabigatran, with and without Aspirin, Compared to Warfarin) trial, were used to indirectly compare the newer anticoagulants regarding efficacy and safety end points using a random effects model, which was performed by William L. Baker, PharmD, Assistant Professor of Pharmacy, University of Connecticut Schools of Pharmacy and Medicine, Farmington, and colleagues.
When compared with dabigatran, apixaban was associated with 26% lower odds for major bleeding and 42% lower odds for GI bleeding.
In comparing dabigatran and riv - aroxaban, the odds of the composite outcome of stroke or systemic embolism was 25% lower with dabigatran, as were the odds for ischemic stroke (33% lower) and hemorrhagic stroke (55% lower).
Compared with rivaroxaban, apixaban was associated with 32% lower odds for a major bleeding event, but rivaroxaban was superior in preventing systemic emboli by nearly 400%.
The researchers concluded head-to-head clinical trials are needed to confirm these findings.