What are the outcomes of edoxaban (Savaysa) in elderly patients with atrial fibrillation (AF) for stroke prevention?

Outcomes of Edoxaban in Elderly AF Patients for Stroke Prevention

Edoxaban 30 mg once daily is the preferred dosing strategy for elderly patients (≥80 years) with atrial fibrillation, as it provides effective stroke prevention with a significantly lower bleeding risk compared to higher doses or warfarin. 1

Efficacy and Safety Profile in Elderly AF Patients

Stroke Prevention Efficacy

• In elderly patients (≥80 years) with AF, edoxaban demonstrates effective stroke prevention:
  • The ENGAGE AF-TIMI 48 trial showed edoxaban was non-inferior to warfarin for preventing stroke and systemic embolism 2
  • In patients ≥80 years, the 30 mg dose showed comparable efficacy to warfarin for stroke prevention without increased ischemic events 1
  • The ELDERCARE-AF trial demonstrated that even a lower 15 mg dose was superior to placebo in very elderly Japanese patients (≥80 years), with an annualized stroke/systemic embolism rate of 2.3% vs 6.7% with placebo 3

Bleeding Risk Profile

• Bleeding risk is a critical consideration in elderly AF patients:
  • Major bleeding was significantly lower with edoxaban 30 mg compared to warfarin in patients ≥80 years (HR 0.59; 95% CI, 0.45-0.77; P<0.001) 1
  • When comparing edoxaban doses in elderly patients without dose-reduction criteria, the 60 mg dose showed 57% more major bleeding events than the 30 mg dose (HR 1.57; 95% CI, 1.04-2.38; P=0.03) 1
  • Gastrointestinal bleeding was particularly increased with the 60 mg dose compared to 30 mg (HR 2.24; 95% CI, 1.29-3.90; P=0.004) 1

Mortality Outcomes

• Edoxaban 30 mg demonstrated favorable mortality outcomes in elderly patients:
  • Lower rates of death compared to warfarin (HR 0.83; 95% CI, 0.70-1.00; P=0.046) 1
  • Better net clinical outcome (composite of death, stroke/systemic embolism, and major bleeding) compared to warfarin (HR 0.78; 95% CI, 0.68-0.91; P=0.001) 1

Dosing Considerations for Elderly AF Patients

Standard Dosing Recommendations

• The FDA-approved standard dose of edoxaban is 60 mg once daily for most AF patients 4
• Dose reduction to 30 mg once daily is recommended for patients with:
  • CrCl 15-50 mL/min
  • Body weight ≤60 kg
  • Concomitant use of certain P-gp inhibitors 4

Age-Specific Dosing Considerations

• For elderly patients (≥80 years), recent evidence supports using the 30 mg dose even in the absence of standard dose-reduction criteria 1
• Pharmacodynamic studies show that factor Xa inhibition with 30 mg in elderly patients is comparable to 60 mg in younger patients, suggesting similar anticoagulant effect with lower bleeding risk 1

Implementation in Clinical Practice

Risk Assessment

• Before initiating edoxaban in elderly AF patients:
  • Calculate stroke risk using CHA2DS2-VASc score (age ≥75 years adds 2 points) 2
  • Assess bleeding risk using HAS-BLED score (age >65 years adds 1 point) 2
  • Calculate creatinine clearance using Cockcroft-Gault equation (required for dosing decisions) 4

Monitoring Recommendations

• Regular monitoring of renal function is essential in elderly patients:
  • Edoxaban is 50% renally excreted 4
  • Renal function should be evaluated before initiation and at least annually 2
  • More frequent monitoring may be needed in patients with fluctuating renal function 2

Special Considerations

• Edoxaban should not be used in patients with CrCl >95 mL/min (rare in elderly) due to reduced efficacy 4
• Edoxaban is not recommended in patients with end-stage renal disease (CrCl <15 mL/min) or on dialysis 4
• Avoid concomitant use of NSAIDs, aspirin, or other antiplatelet agents when possible, as these increase bleeding risk 2

Common Pitfalls and Caveats

• Inappropriate underdosing: While 30 mg is appropriate for most elderly patients, using doses below 30 mg (except in specific clinical trials like ELDERCARE-AF) is not supported by guidelines 2
• Failure to adjust for renal function: Elderly patients often have declining renal function that may not be reflected in serum creatinine alone; always calculate CrCl 4
• Discontinuation without bridging: Abrupt discontinuation increases stroke risk; follow appropriate transition protocols when switching anticoagulants 4
• Overlooking drug interactions: P-gp inhibitors can increase edoxaban levels and may require dose adjustment 4
• Inadequate follow-up: Regular monitoring of renal function, bleeding signs, and medication adherence is essential in elderly patients 2

In conclusion, edoxaban represents an effective option for stroke prevention in elderly AF patients with a favorable safety profile when appropriately dosed. The 30 mg dose appears to offer the optimal balance of efficacy and safety in patients ≥80 years old, even without traditional dose-reduction criteria.