In a patient with systolic heart failure who cannot afford Tresto (sacubitril/valsartan), which is more suitable, lisinopril or losartan?

Lisinopril is Superior to Losartan for Systolic Heart Failure When Tresto is Unaffordable

For patients with systolic heart failure who cannot afford sacubitril/valsartan (Tresto), lisinopril is the preferred alternative over losartan due to stronger evidence supporting ACE inhibitors as first-line therapy and better mortality outcomes. 1

Rationale for ACE Inhibitor Preference

ACE inhibitors have been extensively studied in heart failure with reduced ejection fraction (HFrEF) and are considered first-line therapy when angiotensin receptor neprilysin inhibitors (ARNIs) like sacubitril/valsartan are not an option:

• ACE inhibitors have demonstrated significant mortality benefits in multiple landmark trials, with lisinopril specifically showing dose-dependent benefits in the ATLAS trial 1, 2
• Higher doses of lisinopril (32.5-35 mg daily) reduced the risk of death or hospitalization by 12% compared to lower doses 2
• ACE inhibitors are recommended as Class I, Level A evidence for all symptomatic HFrEF patients according to ESC guidelines 1

Comparing ACE Inhibitors vs ARBs

While both medication classes block the renin-angiotensin-aldosterone system (RAAS), important differences exist:

• ARBs (including losartan) are generally considered alternatives only when ACE inhibitors are not tolerated 1
• The ELITE II trial directly compared losartan to captopril and found no significant difference in mortality or sudden cardiac death, but did not demonstrate superiority of losartan 1, 3
• The CHARM-Alternative trial showed benefit with candesartan in ACE inhibitor-intolerant patients, but this doesn't establish ARB superiority over ACE inhibitors 1

Dosing Considerations

If selecting lisinopril:

• Starting dose: 2.5-5 mg once daily
• Target dose: 20-35 mg once daily 1

If losartan must be used (e.g., due to ACE inhibitor intolerance):

• Starting dose: 25-50 mg once daily
• Target dose: 150 mg once daily 1, 4

Important Clinical Considerations

1. Titration strategy: Regardless of which agent is chosen, uptitration to target doses is crucial for maximizing mortality benefit 1

2. Monitoring requirements:

   • Blood pressure and heart rate at each visit
   • Renal function and potassium levels, especially in patients with CKD 1, 4
   • Signs/symptoms of heart failure

3. Common side effects to monitor:

   • ACE inhibitors: Dry cough (most common reason for switching to ARB), angioedema, hypotension, hyperkalemia, renal dysfunction
   • ARBs: Hypotension, hyperkalemia, renal dysfunction (but no cough)

Special Circumstances

In certain situations, losartan might be considered:

• Patients with intolerable ACE inhibitor-induced cough
• History of angioedema with ACE inhibitors
• Specific comorbidities where ARBs have shown benefit (e.g., isolated systolic hypertension with LVH) 5

Pitfalls to Avoid

1. Underdosing: Many patients receive suboptimal doses of RAAS blockers. Always aim for target doses shown to improve outcomes 1, 4

2. Triple RAAS blockade: Never combine ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists due to increased risk of hyperkalemia and renal dysfunction 1

3. Discontinuation during minor symptom changes: Temporary side effects like mild dizziness can often be managed through patient education rather than dose reduction 4

4. Failure to consider cost-effective alternatives: While Tresto (sacubitril/valsartan) has superior outcomes, generic ACE inhibitors like lisinopril provide substantial benefit at much lower cost

In conclusion, when sacubitril/valsartan is unaffordable, lisinopril should be the preferred agent for patients with systolic heart failure, with losartan reserved for those who cannot tolerate ACE inhibitors.