If a woman with heart failure cannot afford sacubitril/valsartan, what affordable alternative guideline‑directed medications should be used, especially if she is planning a future pregnancy?

Affordable Alternative to Sacubitril/Valsartan for Women with Heart Failure

If a woman with heart failure cannot afford sacubitril/valsartan, she should be treated with the combination of an ACE inhibitor (such as enalapril, captopril, or benazepril) plus a beta-blocker (preferably metoprolol) plus a mineralocorticoid receptor antagonist (spironolactone or eplerenone), which represents the foundational guideline-directed medical therapy for heart failure with reduced ejection fraction and costs significantly less. 1

Core Affordable GDMT Regimen

The 2022 AHA/ACC/HFSA guidelines establish that while sacubitril/valsartan is now part of the four-pillar therapy for HFrEF, the traditional three-drug combination remains highly effective and evidence-based 1. This regimen includes:

• ACE inhibitor: Enalapril, captopril, or benazepril are preferred choices
• Beta-blocker: Metoprolol (beta-1 selective) is the preferred agent
• Mineralocorticoid receptor antagonist (MRA): Spironolactone or eplerenone

These medications have decades of proven mortality and morbidity reduction in heart failure and are available as generics at substantially lower cost than sacubitril/valsartan 2.

Special Considerations for Future Pregnancy Planning

This is critically important: If she is planning a future pregnancy, the medication strategy must be modified because ACE inhibitors, ARBs (including the valsartan component of sacubitril/valsartan), and mineralocorticoid receptor antagonists are all contraindicated during pregnancy due to fetotoxicity 3, 4.

Pre-Pregnancy Treatment Strategy:

• Continue ACE inhibitor + beta-blocker + MRA until pregnancy is confirmed
• Immediately upon pregnancy detection, discontinue the ACE inhibitor and MRA
• Switch to hydralazine plus nitrates for afterload reduction during pregnancy 3
• Continue beta-blocker (metoprolol preferred; avoid atenolol) with neonatal monitoring for 24-48 hours after delivery 3

During Pregnancy:

• Hydralazine + nitrates replace ACE inhibitors/ARBs for afterload reduction
• Beta-blocker (metoprolol) continues if tolerated
• Diuretics (furosemide, hydrochlorothiazide) only if pulmonary congestion is present
• Avoid all ACE inhibitors, ARBs, and aldosterone antagonists 3

Post-Delivery:

Once hemodynamically stable after delivery, immediately resume the full GDMT regimen (ACE inhibitor + beta-blocker + MRA) 3.

Cost-Effectiveness Evidence

Research demonstrates that out-of-pocket costs significantly impact medication adherence. At $100/month, only 33% of patients were willing to take sacubitril/valsartan compared to 85% at $10/month 5. Generic ACE inhibitors, beta-blockers, and MRAs typically cost $10-30/month total, making them accessible alternatives.

Clinical Outcomes with Standard GDMT

While sacubitril/valsartan shows superior outcomes compared to ACE inhibitors alone, the traditional three-drug combination (ACE inhibitor + beta-blocker + MRA) remains highly effective at reducing mortality and hospitalizations in HFrEF 2, 6. The key is optimizing doses of all three medication classes rather than using suboptimal doses.

Practical Implementation Algorithm

1. Start ACE inhibitor (e.g., enalapril 2.5 mg twice daily), titrate to target dose
2. Add beta-blocker (e.g., metoprolol succinate 12.5-25 mg daily), titrate slowly
3. Add MRA (spironolactone 12.5-25 mg daily), monitor potassium and renal function
4. Monitor closely for hypotension, hyperkalemia, and worsening renal function
5. If pregnancy occurs: Stop ACE inhibitor and MRA immediately, switch to hydralazine/nitrates

Critical Pregnancy Warning

The FDA black box warning for sacubitril/valsartan explicitly states that drugs acting on the renin-angiotensin system can cause injury and death to the developing fetus 4. This same warning applies to all ACE inhibitors and ARBs. Women of childbearing potential must have pregnancy testing and counseling before starting these medications, and they must be discontinued immediately when pregnancy is detected 4.

Breastfeeding Considerations:

• If breastfeeding is planned, benazepril, captopril, or enalapril are preferred ACE inhibitors 3
• Sacubitril/valsartan is not recommended during breastfeeding 4
• Beta-blockers (metoprolol) can be continued with neonatal monitoring 3

Common Pitfalls to Avoid

• Do not use atenolol as the beta-blocker choice, especially in pregnancy planning 3
• Do not continue ACE inhibitors or MRAs once pregnancy is confirmed
• Do not delay switching to hydralazine/nitrates in pregnancy
• Do not use aldosterone antagonists during pregnancy (spironolactone has antiandrogenic effects) 3
• Monitor potassium levels closely when combining ACE inhibitors with MRAs

The affordable alternative regimen provides substantial clinical benefit and allows for safe transition to pregnancy-compatible medications when needed.