In an adult with uncomplicated primary hypertension and no contraindications, how do amlodipine and losartan compare and rank in the treatment hierarchy, and what are their usual starting doses?

Amlodipine vs. Losartan: Treatment Hierarchy and Starting Doses

For uncomplicated primary hypertension, both amlodipine (a calcium channel blocker) and losartan (an ARB) are equally acceptable first-line agents, with the choice depending primarily on patient race and specific clinical characteristics. 1

Treatment Hierarchy by Patient Population

For Black Patients

• Amlodipine is preferred over losartan as first-line therapy, as thiazide diuretics and calcium channel blockers are more effective than ARBs in this population due to lower renin levels. 1, 2
• The 2017 ACC/AHA guidelines explicitly recommend thiazide diuretics or CCBs (like amlodipine) for Black patients without heart failure or chronic kidney disease. 1

For Non-Black Patients

• Both agents are equally acceptable as first-line monotherapy for stage 1 hypertension. 1
• The guidelines show no significant differences between ACE inhibitors, ARBs, and CCBs for prevention of cardiovascular events, stroke, or mortality in head-to-head comparisons. 1
• Thiazide diuretics remain the slight preference when no compelling indications exist, as they demonstrated superior outcomes for heart failure prevention compared to CCBs in network meta-analyses. 1

Priority Ranking for Uncomplicated Hypertension

1. Thiazide-type diuretics (chlorthalidone preferred)

• Strongest evidence for cardiovascular event reduction, particularly heart failure prevention. 1
• Superior to CCBs for heart failure prevention in direct comparisons. 1

2. Amlodipine (CCB)

• Equivalent to ARBs for most cardiovascular outcomes. 1
• Preferred over losartan in Black patients. 1
• More effective blood pressure reduction than losartan in direct comparisons (16.1 vs. 13.7 mmHg systolic reduction). 3

3. Losartan (ARB)

• Equivalent efficacy to amlodipine in non-Black patients. 1
• Particularly beneficial when compelling indications exist: chronic kidney disease, diabetes with nephropathy, heart failure, or ACE inhibitor-induced cough. 4, 2
• Less effective than amlodipine in Black and Hispanic populations (41.4% vs. 62.5% response rate in African Americans). 3

Standard Starting Doses

Amlodipine

• Starting dose: 5 mg once daily 4, 5
• Maximum dose: 10 mg once daily 4, 5
• Titration: Increase to 10 mg after 2-4 weeks if blood pressure remains uncontrolled. 4

Losartan

• Starting dose: 50 mg once daily 4, 2, 3
• Maximum dose: 100 mg once daily 4
• Titration: Increase to 100 mg after 2-4 weeks if blood pressure remains uncontrolled. 4

Comparative Efficacy Evidence

Blood Pressure Reduction

• Amlodipine demonstrates greater blood pressure lowering than losartan in direct head-to-head trials: systolic reduction of 16.1 vs. 13.7 mmHg (p=0.018) and diastolic reduction of 12.6 vs. 10.3 mmHg (p=0.002). 3
• Amlodipine achieved better 24-hour blood pressure control, particularly during evening and morning hours (trough-to-peak ratio 62% vs. 55%, p<0.05). 6
• Response rates favored amlodipine: 63.8% vs. 55.1% achieved diastolic BP ≤90 mmHg. 3

Cardiovascular Outcomes

• Network meta-analyses show no significant differences between CCBs and ARBs for prevention of cardiovascular events, stroke, or all-cause mortality. 1
• Both classes are inferior to thiazide diuretics for heart failure prevention. 1

When to Choose Amlodipine Over Losartan

• Black patients (stronger evidence for efficacy) 1, 3
• Hispanic patients (67.7% vs. 53.5% response rate) 3
• Elderly patients with volume-dependent hypertension 4
• When 24-hour blood pressure control is critical (longer duration of action) 6
• Stage 2 hypertension requiring rapid control (greater magnitude of BP reduction) 3, 7

When to Choose Losartan Over Amlodipine

• Chronic kidney disease (renoprotective effects) 4, 2
• Diabetes with nephropathy (slows progression of kidney disease) 4, 2
• Heart failure with reduced ejection fraction (mortality benefit) 4, 2
• ACE inhibitor-induced cough (alternative RAS blockade without cough) 2
• Patients intolerant to amlodipine-related peripheral edema 4

Combination Therapy Considerations

For Stage 2 Hypertension (BP ≥140/90 mmHg or >20/10 mmHg above target)

• Initiate with two agents from different classes rather than monotherapy. 1
• Preferred combinations:
  • Amlodipine + losartan (complementary mechanisms: vasodilation + RAS blockade) 4, 5
  • Amlodipine + thiazide diuretic (especially for Black patients) 1, 4
  • Losartan + thiazide diuretic 4

Triple Therapy Algorithm

• If uncontrolled on dual therapy, add the third agent: ARB + CCB + thiazide diuretic. 1, 4, 5
• This represents the evidence-based triple therapy targeting volume reduction, vasodilation, and RAS blockade. 4, 5

Critical Monitoring Parameters

For Amlodipine

• Monitor for dose-related peripheral edema (more common in women). 4, 5
• Edema may be attenuated when combined with an ARB or ACE inhibitor. 4
• Use long-acting formulations only; avoid immediate-release nifedipine. 5

For Losartan

• Check serum potassium and creatinine 2-4 weeks after initiation to detect hyperkalemia or acute kidney injury. 4, 2
• Monitor more closely when combined with diuretics or in patients with chronic kidney disease. 4, 2

Blood Pressure Targets

• Primary target: <130/80 mmHg for most adults 1, 4
• Minimum acceptable: <140/90 mmHg 1
• Reassess within 2-4 weeks after initiating or adjusting therapy. 4
• Achieve target within 3 months of treatment initiation or modification. 4

Common Pitfalls to Avoid

• Never combine losartan with an ACE inhibitor—dual RAS blockade increases hyperkalemia and acute kidney injury without cardiovascular benefit. 1, 4, 5, 2
• Do not use non-dihydropyridine CCBs (diltiazem, verapamil) in patients with heart failure due to negative inotropic effects. 4, 5
• Do not delay combination therapy in stage 2 hypertension—initiate two agents immediately. 1
• Verify medication adherence before assuming treatment failure, as non-adherence is the most common cause of apparent resistance. 4
• Do not rely on monotherapy dose escalation when combination therapy is more effective. 4