Patients with a genetic sensitivity to warfarin may have higher rates of bleeding during the first several months of treatment and could benefit from therapy with an alternate anticoagulant medication, reports a new study in The Lancet.
Marc S. Sabatine, MD, MPH, of Brigham and Women’s Hospital in Boston, and colleagues analyzed data from the international, randomized, double-blind ENGAGE AF-TIMI 48 trial comparing 60mg of edoxaban daily, 30mg of edoxaban daily, or warfarin to prevent the formation of blood clots in patients with atrial fibrillation. The more than 14,000 study participants were categorized as normal responders, sensitive responders, or highly sensitive responders based on genetic makeup (CYP2C9 and VKORC1 genotypes) and followed for up to almost three years.
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Sensitive and highly sensitive responders who received warfarin had significantly higher rates of bleeding and spent greater proportions of time over-anticoagulated in the first 90 days of treatment vs. normal responders. During this early time period, edoxaban was more effective than warfarin at reducing bleeding in sensitive and highly sensitive responders. The reduction in bleeding risk with edoxaban vs. warfarin was similarly beneficial across genotypes after 90 days.
The application of genotypes for appropriate anticoagulant therapy could help to identify those patients who are more likely to experience early bleeding with warfarin and would benefit from an alternative anticoagulant medication, the authors conclude.
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