The direct oral anticoagulant (DOAC) edoxaban is superior to warfarin for mitigating stroke risk in Latin American patients with atrial fibrillation (AFib), according to results of the ENGAGE AF-TIMI trial, published this month in the Journal of the American College of Cardiology.
The project, spearheaded by Ramón Corbalán, MD, of Pontificia Universidad Católica de Chile in Santiago, Chile, compared the efficacy of both higher-dose and lower-dose edoxaban in reducing stroke and systemic embolism against warfarin—historically a gold standard for preventing thromboembolic events in high-risk patients with AFib.
The focus shifted from warfarin in 2010, Sergio J. Dubner, MD, and Nicolas Martinenghi, MD, wrote in a related JACC editorial, when the FDA approved an oral direct thrombin inhibitor, dabigatran exilate, for the same purpose. Rivaroxaban, apixaban and edoxaban followed suit.
“These DOACs represent a major advance in the treatment of AF and provide several advantages, including rapid onset and offset of action, no need for routine monitoring of anticoagulation intensity, few interactions with other drugs or food and predictable pharmacokinetics,” Dubner and Martinenghi wrote. “In the pivotal studies, the DOACs were at least as effective as warfarin, and rates of intracranial hemorrhagic events were significantly lower.”
In a similar study of Korean patients published a month ago in JACC, edoxaban users with AF saw a 31 percent reduced risk of ischemic stroke compared to patients who took warfarin.
For their work, Corbalán and his team designed an international, double-blind study of Latin American patients—some of whom lived in South America and others who didn’t—with atrial fibrillation, randomizing 2,661 Latin American patients and 18,444 non-Latin Americans to either 60 milligrams of edoxaban daily, 30 milligrams of edoxaban daily or warfarin, dose-adjusted to an International Normalized Ratio of 2.0 to 3.0.
Compared to those using warfarin, Latin American edoxaban users saw a 36 percent decreased risk of stroke, a 29 percent reduced risk of major bleeding and a 22 percent decreased risk of cardiovascular death, according to the study. Latin American patients tended to be older at baseline and have a higher proportion of permanent AF, hypertension, heart failure and left ventricular ejection fractions, and the authors said they also had lower creatinine clearance and were less likely to be treated with beta-blockers and statins.
After an average three years of follow-up, Corbalán et al. found both groups on edoxaban saw similar overall risks for stroke and systemic embolism, though non-Latin American patients fared slightly worse than their Hispanic counterparts. Non-Latin American edoxaban users saw risk reductions of 9 percent for stroke, 18 percent for major bleeding and 12 percent for CV death versus non-Latin American warfarin users.
There was also a much greater reduction in hemorrhagic stroke with edoxaban among Latin American patients than among non-Latin Americans, the authors wrote, with the former group reporting an 84 percent decreased risk compared to the latter group’s 36 percent reduction.
In Latin America and abroad, edoxaban appeared to reduce risk of stroke, major bleeding and cardiovascular death with better results than warfarin.
“Prospective practice-based data from Latin American patients would also be helpful to confirm the findings of the randomized trial,” Dubner and Martinenghi said. “At this point, however, the new report provides an important contemporary picture of the response of Latin American patients to antithrombotic therapy and provides encouragement to those favoring selection of a target-specific anticoagulant over warfarin for patients with atrial fibrillation at risk for stroke.”