For a patient with hypertension and cardiac disease (e.g., heart failure, post‑myocardial infarction, or diabetic kidney disease), is losartan or amlodipine the preferred medication?

Losartan vs Amlodipine for Heart Patients

For patients with heart failure, post-myocardial infarction, or diabetic nephropathy, losartan is the preferred first-line agent; amlodipine should be reserved for blood pressure control after ACE inhibitors/ARBs, beta-blockers, and diuretics have been initiated. 1, 2

Evidence-Based Selection Algorithm

Heart Failure (Systolic Dysfunction)

• Losartan (or other ARBs) is strongly preferred as part of guideline-directed medical therapy, alongside diuretics, beta-blockers, and aldosterone antagonists 1
• Amlodipine should be avoided as first-line therapy in heart failure with reduced ejection fraction due to lack of mortality benefit 1, 3
• Add amlodipine only if hypertension persists after optimizing neurohormonal blockade (ACE inhibitor/ARB + beta-blocker + diuretic), particularly if angina is present 1

Post-Myocardial Infarction

• Losartan (or ACE inhibitors) reduces recurrent MI and death when started early after myocardial infarction 1
• The ELITE II trial showed losartan was equivalent to captopril for mortality in heart failure patients, with better tolerability (fewer discontinuations: 9.7% vs 14.7%, p<0.001) 4
• Amlodipine is equally effective for chronic coronary disease when blood pressure control is the primary goal, as demonstrated in ALLHAT 1, 3
• Preferred sequence: Start beta-blocker + ACE inhibitor/ARB, then add amlodipine if blood pressure remains elevated 1

Diabetic Nephropathy with Proteinuria

• Losartan is FDA-indicated for diabetic nephropathy with elevated creatinine and proteinuria ≥300 mg/g, reducing progression to end-stage renal disease 2
• Losartan reduces doubling of serum creatinine and need for dialysis in type 2 diabetics with hypertension 2
• Amlodipine has no specific renoprotective indication in diabetic nephropathy 3

Uncomplicated Hypertension with Cardiac Disease

• Both agents are acceptable first-line options for blood pressure reduction in stable coronary disease 1, 3
• The VALUE trial showed no difference in cardiac mortality between valsartan and amlodipine (hazard ratio 1.0), though amlodipine achieved slightly lower blood pressure 1, 5
• Amlodipine may have a slight edge for stroke prevention (25% reduction vs beta-blockers in LIFE, though this compared losartan to atenolol, not amlodipine directly) 1

Comparative Safety and Tolerability

Losartan Advantages

• Significantly fewer discontinuations due to adverse effects compared to ACE inhibitors (9.7% vs 14.7%) 4
• Minimal cough (0.3% vs 2.7% with captopril) 4
• Lower angioedema risk than ACE inhibitors (one less case per 500 patients) 6
• Well-tolerated in diabetics without adverse metabolic effects 7

Losartan Monitoring Requirements

• Monitor serum creatinine and potassium at least annually, more frequently in chronic kidney disease 3, 7
• Risk of hyperkalemia increases when combined with potassium supplements or aldosterone antagonists 6
• Avoid combining with ACE inhibitors—the VALIANT study showed increased adverse events without added mortality benefit 1

Amlodipine Considerations

• Dose-related peripheral edema is common; can be mitigated by combining with ARB 7, 3
• Contraindicated as first-line in heart failure with reduced ejection fraction unless needed for refractory hypertension or angina 1, 3
• No adverse metabolic effects on glucose or lipids 7
• Avoid short-acting dihydropyridines (e.g., immediate-release nifedipine) due to reflex tachycardia 1, 3

Critical Pitfalls to Avoid

• Never use amlodipine as monotherapy in systolic heart failure—it provides no mortality benefit and should only be added after ACE inhibitor/ARB, beta-blocker, and diuretic 1, 3
• Do not combine losartan with ACE inhibitors—this increases hyperkalemia and renal dysfunction without improving outcomes 1, 6
• In Black patients without heart failure or nephropathy, amlodipine is more effective than losartan for preventing stroke and heart failure 3, 8
• Titrate losartan to target doses (150 mg daily for heart failure, higher than the 50 mg commonly used for hypertension) to achieve mortality benefits 1
• Monitor blood pressure closely when initiating losartan post-MI, as hypotension is more common than with amlodipine 6

Practical Implementation

Starting Losartan

• Initial dose: 25–50 mg once daily 2
• Target dose for heart failure: 150 mg daily (higher than hypertension dosing) 1
• Target dose for diabetic nephropathy: Titrate to maximum tolerated dose 2
• Check creatinine and potassium within 2–4 weeks of initiation 3

Starting Amlodipine

• Initial dose: 5 mg once daily 3
• Target dose: 10 mg once daily if blood pressure remains >130/80 mmHg 3
• Assess for pedal edema at follow-up visits 3, 7

Combination Therapy

• Losartan + amlodipine is effective when monotherapy fails, with amlodipine reducing losartan-induced hyperkalemia risk and losartan reducing amlodipine-induced edema 3, 7
• Preferred triple therapy: Losartan + amlodipine + thiazide diuretic for resistant hypertension 3, 9