What medication can be added to a regimen of enalapril (Angiotensin-Converting Enzyme (ACE) inhibitor) and amlodipine (Calcium Channel Blocker (CCB)) for a patient with Heart Failure with Reduced Ejection Fraction (HFrEF) and atrial fibrillation (AF) to decrease AF burden?

Sacubitril/Valsartan is the Optimal Addition for HFrEF with Atrial Fibrillation

Sacubitril/valsartan 49/51 mg tablet twice daily is the most appropriate medication to add to the current regimen of enalapril and amlodipine for this 68-year-old female with atrial fibrillation and HFrEF to decrease AF burden while improving mortality outcomes.

Rationale for Sacubitril/Valsartan

The 2017 ACC/AHA/HFSA guidelines and 2021 update recommend sacubitril/valsartan (ARNI) as a replacement for ACE inhibitors in patients with HFrEF to reduce cardiovascular mortality and heart failure hospitalizations 1. This recommendation is particularly relevant for this patient who:

1. Has HFrEF with persistent symptoms (as evidenced by uncontrolled hypertension)
2. Has concomitant atrial fibrillation
3. Is currently on an ACE inhibitor (enalapril) that can be replaced with ARNI

Benefits of Sacubitril/Valsartan for This Patient:

• Improved Mortality and Morbidity: Sacubitril/valsartan has demonstrated superior outcomes compared to ACE inhibitors in HFrEF patients 2
• Blood Pressure Control: The patient's current BP readings (140-155/85-90 mmHg) are above the recommended target of <130/80 mmHg for HFrEF patients 1
• Atrial Fibrillation Management: The 2019 ESC guidelines specifically recommend sacubitril/valsartan for patients with HFrEF and diabetes, noting its benefit in heart failure management 1
• Preservation of Other GDMT: Initiation of sacubitril/valsartan does not lead to discontinuation of other guideline-directed medical therapies 3

Implementation Strategy

1. Discontinue enalapril: Stop enalapril at least 36 hours before initiating sacubitril/valsartan to minimize angioedema risk 4

2. Initial dosing:

   • Start with 49/51 mg twice daily (the recommended starting dose for patients already on ACE inhibitors) 1
   • If concerns about hypotension exist, a very low dose of 24/26 mg twice daily can be initiated with subsequent up-titration 5

3. Monitoring:

   • Check blood pressure, renal function, and potassium levels within 1-2 weeks of initiation
   • Target dose is 97/103 mg twice daily if tolerated 1

4. Continue amlodipine: Maintain current calcium channel blocker therapy as it complements RAAS blockade

Comparison with Other Options

• Eplerenone: While eplerenone (MRA) is beneficial in HFrEF, it should be added to GDMT including ACE inhibitors/ARBs/ARNIs, not as a replacement. It has less evidence specifically for AF burden reduction compared to sacubitril/valsartan 1.

• Verapamil: Not recommended in HFrEF due to negative inotropic effects that can worsen heart failure symptoms.

• Clonidine: Not a first-line agent for HFrEF and has no specific evidence for AF burden reduction.

Clinical Considerations and Caveats

• Monitor for hypotension: Sacubitril/valsartan can cause symptomatic hypotension, especially in patients >75 years old or with low baseline systolic BP

• Renal function: Ensure eGFR >30 mL/min/1.73m² before initiation 6

• Potassium levels: Monitor potassium regularly, especially if considering adding an MRA in the future

• Angioedema risk: Do not administer within 36 hours of ACE inhibitor discontinuation 4

• Cost considerations: Sacubitril/valsartan may be more expensive than other options, but its clinical benefits justify the cost in appropriate patients

Conclusion

For this 68-year-old female with HFrEF, atrial fibrillation, and uncontrolled hypertension on enalapril and amlodipine, transitioning from enalapril to sacubitril/valsartan represents the optimal therapeutic strategy to reduce AF burden while simultaneously improving heart failure outcomes and blood pressure control.