What is the preferred initial treatment option between Losartan (losartan) and Enalapril (enalapril) for an adult or geriatric patient with hypertension or heart failure?

Losartan vs Enalapril: Treatment Selection

Primary Recommendation

For heart failure with reduced ejection fraction (HFrEF), ACE inhibitors like enalapril should be the initial choice, with losartan reserved for patients who cannot tolerate ACE inhibitors due to cough or angioedema. 1 For hypertension alone, both agents are acceptable first-line options, though enalapril may provide superior cardiovascular protection. 1

Heart Failure Management

First-Line Therapy

• ACE inhibitors (enalapril) are the preferred initial renin-angiotensin system blocker for HFrEF, as they have the most robust mortality and morbidity reduction data. 1
• Enalapril demonstrated significant reductions in hospitalizations and mortality in landmark trials, establishing it as the gold standard comparator. 1
• ARBs like losartan should only be used when ACE inhibitors are not tolerated, specifically due to cough or angioedema. 1

Critical Dosing Considerations

• Standard losartan 50 mg daily appears inferior to ACE inhibitors for mortality reduction in heart failure. 1, 2
• The HEAAL trial demonstrated that losartan 150 mg daily was superior to 50 mg daily, with a 10% relative risk reduction in death or heart failure hospitalization. 1
• If losartan is used for heart failure, target the 150 mg daily dose (though this exceeds the FDA-approved dose for heart failure in the US). 1, 2
• For enalapril, target 10 mg twice daily as used in PARADIGM-HF. 1

Tolerability Profile

• Enalapril carries a significantly higher risk of dry cough (risk ratio 2.88) compared to losartan. 3
• Cough occurred in approximately 30% of enalapril-treated patients versus minimal rates with losartan in comparative trials. 4, 3
• Both agents have similar risks of angioedema, though ARBs have a lower incidence; however, patients with ACE inhibitor-induced angioedema can still develop angioedema with ARBs, so use caution. 1

Hypertension Management

Comparative Efficacy

• Both agents provide similar blood pressure reduction in mild-to-moderate hypertension. 5, 4, 3
• Losartan demonstrated 62% response rate (DBP <90 mmHg) versus 40% for enalapril in one trial, though this was not consistently replicated. 5
• For hypertensive patients with left ventricular hypertrophy, losartan has specific outcome benefits, reducing stroke risk by 25% and cardiovascular events by 13% compared to atenolol in the LIFE trial. 1, 6

Left Ventricular Hypertrophy Regression

• Losartan achieved superior LVH regression (21.7 g/m²) compared to atenolol (17.7 g/m²) in the LIFE trial echocardiographic substudy. 1, 6
• However, ACE inhibitors as a class showed the most effective LVH regression (13.3% reduction) in meta-analysis of 39 trials. 1
• The FDA specifically indicates losartan for stroke risk reduction in hypertensive patients with LVH, though this benefit does not apply to Black patients. 7

Diabetic Nephropathy

Specific Indication

• Losartan is FDA-approved for diabetic nephropathy in type 2 diabetes with elevated serum creatinine and proteinuria (urinary albumin-to-creatinine ratio ≥300 mg/g). 7
• Losartan reduces progression to doubling of serum creatinine or end-stage renal disease in this population. 7
• Both enalapril and losartan have similar effects on renal function and serum uric acid in CKD patients. 3

Practical Implementation Algorithm

Step 1: Identify Primary Indication

• Heart failure with reduced ejection fraction → Start enalapril, target 10 mg twice daily 1
• Hypertension with LVH → Consider losartan 50-100 mg daily 7
• Diabetic nephropathy (type 2) → Losartan 50-100 mg daily 7
• Simple hypertension → Either agent acceptable; enalapril if cost is concern 1

Step 2: Assess Tolerability Factors

• History of ACE inhibitor cough → Switch to losartan 1, 4
• History of angioedema with ACE inhibitor → Consider losartan with extreme caution; wait 36 hours after stopping ACE inhibitor 1
• No prior ACE inhibitor exposure → Start with enalapril for heart failure; either agent for hypertension 1

Step 3: Titration Strategy

• Enalapril: Start 2.5-5 mg twice daily, titrate to 10 mg twice daily 1
• Losartan: Start 25-50 mg daily, titrate to 100 mg daily (or 150 mg for heart failure if tolerated) 1, 2, 7
• Monitor blood pressure, renal function, and potassium at baseline, 1-2 weeks, and with each dose increase 1

Critical Safety Precautions

Shared Contraindications

• Both agents are contraindicated in pregnancy (category D). 7
• Do not combine with other renin-angiotensin system blockers (ACE inhibitors, ARBs, or aliskiren) due to increased adverse events without benefit. 1, 2
• Use caution with potassium >5.0 mEq/L, bilateral renal artery stenosis, or severe renal insufficiency. 1

Angioedema Risk

• Wait 36 hours between stopping an ACE inhibitor and starting an ARB to minimize angioedema risk. 1
• The combination of ACE inhibitors with neprilysin inhibitors causes unacceptable angioedema rates; this same risk exists with ARBs to a lesser degree. 1

Cost-Effectiveness Considerations

• Both agents are available as low-cost generics and provide high value (cost per QALY favorable). 1
• ACE inhibitors have more extensive cost-effectiveness data supporting their use in heart failure. 1
• The similar efficacy and generic availability of both classes support either choice when clinically appropriate. 1