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

## TL;DR

This study found that older patients without dose adjustments for edoxaban had higher bleeding risks compared to standard treatment after heart valve replacement.

## Contribution

The study introduces age-specific insights on edoxaban dose adjustment effects in atrial fibrillation patients post-TAVR.

## Key findings

- Patients aged ≥80 without eDAC had higher major bleeding and gastrointestinal bleeding risks with edoxaban.
- Edoxaban-treated patients without eDAC had nearly double major gastrointestinal bleeding rates compared to those with eDAC.
- Optimized edoxaban dosing for older patients may improve outcomes regardless of eDAC status.

## Abstract

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).

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.

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.

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).

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. (Edoxaban Compared to Standard Care After Heart Valve Replacement Using a Catheter in Patients With Atrial Fibrillation [ENVISAGE-TAVI AF]; NCT02943785)