Lower Dose Anticoagulants Safe and Effective for Elderly Atrial Fibrillation Patients: JAMA

Those randomized to edoxaban, 30 mg per day, had lower major bleeding events compared with either edoxaban, 60 mg per day (in patients without dose-reduction criteria), or warfarin (regardless of dose-reduction criteria), without an offsetting rise in ischemic events, the researchers reported in JAMA Cardiology.

In older patients with atrial fibrillation requiring anticoagulants for stroke prevention, there is a higher risk of bleeding compared to younger patients. Consequently, clinicians often opt for lower-than-recommended doses in older patients despite the limited availability of randomized data supporting this approach.

Against the above background, André Zimerman, Harvard Medical School, Boston, Massachusetts, and colleagues sought to evaluate bleeding and ischemic outcomes in patients 80 years and older with atrial fibrillation receiving edoxaban, 60 mg vs 30 mg, and edoxaban, 30 mg versus warfarin.

The ENGAGE AF-TIMI 48 trial was a parallel-design, double-blind, global clinical trial in which patients with atrial fibrillation were randomized to either one of 2 edoxaban dosing regimens or warfarin. The secondary analysis by Dr. Zimerman et al. focused on patients 80 years or older without dose-reduction criteria receiving edoxaban, 60 mg versus 30 mg, and patients with or without dose-reduction criteria receiving edoxaban, 30 mg, versus warfarin.

Primary composite clinical outcomes were death, stroke, systemic embolism, major bleeding, and each component.

The study led to the following findings:

• The analysis included 2966 patients 80 years and older (mean age, 83 years; 56% males).
• Among 1138 patients 80 years and older without dose-reduction criteria, those receiving edoxaban, 60 mg versus 30 mg, had more major bleeding events (hazard ratio [HR], 1.57), particularly gastrointestinal hemorrhage (HR, 2.24), with no significant difference in efficacy endpoints.
• Findings were supported by analyses of endogenous factor Xa inhibition, a marker of anticoagulant effect, which was comparable between younger patients receiving edoxaban, 60 mg, and older patients receiving edoxaban, 30 mg.
• In 2406 patients 80 years and older with or without dose-reduction criteria, patients receiving edoxaban, 30 mg, versus warfarin had lower rates of the primary net clinical outcome (HR, 0.78), major bleeding (HR, 0.59), and death (HR, 0.83), whereas rates of stroke or systemic embolism were comparable.

"These findings suggest considering lower-dose anticoagulants, such as edoxaban, 30 mg once daily, in all patients 80 years and older with AF irrespective of dose-reduction criteria," the researchers concluded.

Reference:

Zimerman A, Braunwald E, Steffel J, et al. Dose Reduction of Edoxaban in Patients 80 Years and Older With Atrial Fibrillation: Post Hoc Analysis of the ENGAGE AF-TIMI 48 Randomized Clinical Trial. JAMA Cardiol. Published online July 10, 2024. doi:10.1001/jamacardio.2024.1793