What is the preferred choice between losartan (angiotensin II receptor antagonist) and amlodipine (calcium channel blocker) for a patient with hypertension, considering factors such as diabetes, impaired renal function, and treatment goals?

Losartan vs Amlodipine for Hypertension

For most hypertensive patients without specific compelling indications, amlodipine provides superior blood pressure reduction, but losartan should be strongly preferred in patients with diabetes, chronic kidney disease with albuminuria, or left ventricular hypertrophy due to superior outcomes in morbidity and mortality.

Blood Pressure Lowering Efficacy

Amlodipine demonstrates greater blood pressure reduction compared to losartan in head-to-head trials:

• Amlodipine reduces systolic BP by approximately 16.1 mmHg versus 13.7 mmHg with losartan (p=0.018), and diastolic BP by 12.6 mmHg versus 10.3 mmHg (p=0.002). 1
• Response rates are significantly higher with amlodipine, particularly in African Americans (62.5% vs 41.4%, p=0.033) and Hispanic patients (67.7% vs 53.5%, p=0.039). 1
• In the VALUE trial with over 15,000 high-risk hypertensive patients, amlodipine achieved slightly lower blood pressure values than valsartan (an ARB similar to losartan) over 5 years of follow-up. 2

Cardiovascular Outcomes and Mortality

When Losartan is Superior

In patients with left ventricular hypertrophy, losartan reduces major cardiovascular events by 13% and stroke by 25% compared to beta-blockers, despite equivalent blood pressure control. 2, 3

• The LIFE study in over 9,000 hypertensive patients with LVH showed losartan achieved equal blood pressure reduction to atenolol but with significantly better cardiovascular outcomes. 2
• Losartan reduces left ventricular mass by 21.7 g/m² compared to 17.7 g/m² with beta-blockers. 3

When Amlodipine Shows Advantages

In the VALUE trial comparing valsartan (ARB class) to amlodipine:

• Cardiac events and death (primary outcome) were not significantly different between groups, but amlodipine showed a significant reduction in myocardial infarction. 2
• There was a non-significant trend toward lower stroke incidence with amlodipine. 2
• Valsartan showed a trend favoring prevention of heart failure. 2

Diabetes: Losartan is Preferred

For hypertensive patients with diabetes, ACE inhibitors or ARBs (including losartan) are recommended as first-line therapy. 2

• Multiple guidelines from the American Diabetes Association and American Heart Association recommend ACE inhibitors or ARBs as initial treatment for hypertension in diabetic patients. 2
• If one class is not tolerated, the other should be substituted. 2
• Target blood pressure should be <130/80 mmHg for patients with diabetes. 4

Chronic Kidney Disease and Proteinuria: Losartan is Strongly Preferred

Losartan provides superior renoprotection compared to amlodipine, particularly in patients with proteinuria, independent of blood pressure lowering.

Proteinuria Reduction

• Losartan significantly reduces 24-hour urinary protein excretion by 20.7% at 3 months, 35.2% at 6 months, and 35.8% at 12 months, while amlodipine does not change proteinuria. 5
• In patients with baseline proteinuria ≥2 g/day, losartan reduces proteinuria by 47.9% at 12 months. 5
• Losartan decreases urinary albumin excretion from 3,510 mg/24h to 2,684 mg/24h (p<0.01), while amlodipine increases it non-significantly to 3,748 mg/24h. 6

Albuminuria Guidelines

• For patients with urine albumin-to-creatinine ratio ≥300 mg/g, ACE inhibitors or ARBs at maximum tolerated dose are the recommended first-line treatment (Grade A recommendation). 2
• For UACR 30-299 mg/g, ACE inhibitors or ARBs are suggested to reduce risk of progressive kidney disease (Grade B recommendation). 2
• In the absence of albuminuria, ACE inhibitors and ARBs have not shown superior cardioprotection compared to thiazide-like diuretics or dihydropyridine calcium channel blockers. 2

Renal Function Monitoring

• Losartan decreases filtration fraction from 22.8% to 21.2% (p<0.05), indicating reduced intraglomerular pressure, while amlodipine increases it to 23.6%. 6
• Serum creatinine/eGFR and potassium should be monitored at least annually in patients on ACE inhibitors, ARBs, or diuretics. 2
• Continuation of ACE inhibitors or ARBs as kidney function declines to eGFR <30 mL/min/1.73 m² may provide cardiovascular benefit without significantly increasing risk of end-stage kidney disease. 2

Tolerability and Adverse Effects

Losartan demonstrates superior tolerability compared to amlodipine with fewer drug-related adverse events and withdrawals.

• Drug-related adverse events and withdrawals are higher with amlodipine than losartan. 7
• Ankle edema and "any discomfort" increase with amlodipine but not with losartan. 7
• Losartan may cause dizziness upon standing, angioedema, hyperkalemia, headache, and dizziness. 8
• Quality of life measurements (PGWB index) show improvements in some domains with losartan while remaining unchanged with amlodipine. 7

Clinical Algorithm for Selection

Choose Losartan When:

• Diabetes is present 2
• Albuminuria exists (UACR ≥30 mg/g) 2, 4
• Chronic kidney disease with proteinuria 2, 5, 6
• Left ventricular hypertrophy on ECG 2, 3
• Heart failure risk is elevated 2

Choose Amlodipine When:

• Maximum blood pressure reduction is the priority in uncomplicated hypertension 1
• Patient is African American or Hispanic without diabetes/CKD 1
• Coronary artery disease with need for aggressive BP control 2
• Losartan or ACE inhibitors are not tolerated 2

Common Pitfalls to Avoid:

• Do not use dual RAAS blockade (combining ACE inhibitor with ARB) as this increases adverse events without improving outcomes. 2
• Do not assume equal blood pressure lowering means equal outcomes—organ-specific protection differs between drug classes. 5, 6
• Do not neglect monitoring potassium and renal function when initiating losartan, especially in CKD patients. 2
• Most patients require multiple antihypertensive agents to reach target BP; monotherapy comparison is often academic. 2