What is the role of Apixaban (apixaban) in patients with heart failure with preserved ejection fraction (HFpEF)?

Role of Apixaban in Heart Failure with Preserved Ejection Fraction (HFpEF)

Apixaban is not routinely recommended for patients with HFpEF unless they have atrial fibrillation (AF) with additional risk factors for cardioembolic stroke. 1

Indications for Anticoagulation in HFpEF

Patients with HFpEF and Atrial Fibrillation

• Strong indication: HFpEF with permanent/persistent/paroxysmal AF AND at least one additional risk factor for cardioembolic stroke (history of hypertension, diabetes mellitus, previous stroke or TIA, or age ≥75 years) 1
• Reasonable indication: HFpEF with permanent/persistent/paroxysmal AF even without additional risk factors 1

Patients with HFpEF without Atrial Fibrillation

• No indication: Anticoagulation is not recommended in patients with HFpEF who do not have AF, prior thromboembolic events, or other cardioembolic sources 1

Selection of Anticoagulant in HFpEF with AF

When anticoagulation is indicated in HFpEF patients with AF, apixaban is a preferred option based on:

1. Superior efficacy and safety profile: Apixaban was superior to warfarin for reducing the risk of stroke and systemic embolism in the ARISTOTLE trial, with fewer major bleeding events 2

2. Consistent benefit across heart failure subtypes: In the ARISTOTLE trial, apixaban reduced the risk of stroke or systemic embolism and death more than warfarin in all patient groups, including those with preserved ejection fraction 3

3. Dosing considerations:

   • Standard dose: 5 mg twice daily
   • Reduced dose (2.5 mg twice daily) for patients with at least 2 of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 2

Special Considerations for Apixaban in HFpEF

Renal Function

• Apixaban can be used in patients with reduced renal function
• For patients on dialysis, apixaban may be preferable to warfarin, with standard-dose apixaban (5 mg) showing lower risk of stroke/embolism than low-dose apixaban (2.5 mg) or warfarin 1

Hepatic Function

• No dose adjustment required for mild hepatic impairment (Child-Pugh A)
• Use with caution in moderate hepatic impairment (Child-Pugh B)
• Avoid in severe hepatic impairment (Child-Pugh C) 2

Drug Interactions

• Avoid concomitant use with strong dual inhibitors of CYP3A4 and P-gp
• Dose reduction may be needed with certain medications that increase apixaban levels 2

Comprehensive Management of HFpEF

While anticoagulation with apixaban is important for HFpEF patients with AF, comprehensive management should include:

1. Volume management: Diuretics for symptom relief in volume overload 4

2. First-line disease-modifying therapy: SGLT2 inhibitors (empagliflozin or dapagliflozin) to reduce hospitalizations and improve quality of life 4

3. Additional pharmacological options:

   • Mineralocorticoid receptor antagonists in selected patients 1, 4
   • ARBs for patients with hypertension 1, 4

4. Lifestyle modifications:

   • Supervised exercise training to improve exercise capacity 1, 4
   • Moderate sodium restriction (2-3g/day) 4
   • Weight reduction for overweight/obese patients 4

Pitfalls and Caveats

1. Avoid inappropriate anticoagulation: Do not prescribe apixaban for HFpEF patients without AF, prior thromboembolic events, or other cardioembolic sources 1

2. Monitor for bleeding risks: Regular assessment of bleeding risk is essential when using apixaban, particularly in elderly patients or those with renal impairment

3. Recognize limitations of evidence: Most clinical trials in HFpEF have focused on symptomatic improvement rather than mortality benefits 5, 6, 7, 8

4. Avoid medications that can worsen HF: NSAIDs, most antiarrhythmic drugs, and most calcium channel blockers (except amlodipine) 4

In conclusion, apixaban plays an important role in HFpEF management, but specifically for patients with concomitant AF and additional stroke risk factors. For HFpEF patients without AF, anticoagulation with apixaban is not recommended as part of routine care.