Edoxaban Dose Adjustment and Age-Associated Outcomes in Patients With Atrial Fibrillation Post-Transcatheter Aortic Valve Replacement

Background: 

In ENVISAGE-TAVI AF (EdoxabaN Versus standard of care and theIr effectS on clinical outcomes in pAtients havinG undergonE Transcatheter Aortic Valve Implantation-in Atrial Fibrillation), there were more bleeding events with edoxaban 60 mg than vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) after transcatheter aortic valve replacement (TAVR). 

Objectives: 

This analysis evaluated the impact of edoxaban dose adjustment criteria (eDAC) by age and treatment group (edoxaban vs VKA) on clinical events in patients with AF post-TAVR. Methods: In this ENVISAGE-TAVI AF on-treatment analysis, patients received edoxaban 60 mg once daily—adjusted to 30 mg if they met ≥1 eDAC (creatinine clearance 15 to ≤50 mL/min, body weight ≤60 kg, or concomitant use of potent P-glycoprotein inhibitors)—or VKA. Clinical outcomes were compared between patients with vs without eDAC by age (<80 vs ≥ 80 years) and by treatment group. 

Results: 

Of 1,377 patients, 637 (46%) met eDAC; 740 (54%) did not. Patients with vs without eDAC had significantly higher rates of cardiovascular death (HR: 1.73; 95% CI: 1.01-2.95; P = 0.045). Patients aged ≥80 years without eDAC experienced higher annualized major bleeding (HR: 1.86; 95% CI: 1.04-3.32) and major gastrointestinal bleeding (MGIB) (HR: 3.79; 95% CI: 1.56-9.25) rates with edoxaban vs VKA. Rates of MGIB almost doubled in edoxaban-treated patients without vs with eDAC (8.03%/year vs 4.65%/year). A similar effect was seen in patients aged <80 years without vs with eDAC (4.22%/year vs 2.98%/year). 

Conclusions: 

Patients aged ≥80 years without eDAC were at a higher risk of major bleeding and MGIB events with edoxaban 60 mg vs VKA. An optimized edoxaban dose for octogenarians with AF post-TAVR, regardless of eDAC, may help improve outcomes.