What are the effects of taking lisinopril (Angiotensin-Converting Enzyme (ACE) inhibitor) and amlodipine (Calcium Channel Blocker (CCB)) together for high blood pressure (Hypertension)?

Lisinopril and Amlodipine Combination for Hypertension

The combination of lisinopril (ACE inhibitor) and amlodipine (calcium channel blocker) is highly effective and recommended for hypertension management, particularly when monotherapy fails to achieve blood pressure targets below 130/80 mmHg. 1

Evidence for Combination Therapy

This combination produces superior blood pressure reduction compared to either drug alone, with synergistic effects at both peak and trough drug levels. 2, 3 The additive effect is clinically significant:

• The combination of 2.5 mg amlodipine with 5 mg lisinopril produces greater blood pressure lowering in a higher percentage of patients than individual low doses 2
• At standard doses (amlodipine 5 mg + lisinopril 10 mg), the combination achieves target blood pressure in more patients than monotherapy with either agent 2, 3
• The blood pressure-lowering effect is sustained over 24 hours, making once-daily dosing effective 3

Guideline-Based Rationale

The 2017 ACC/AHA guidelines explicitly support this combination strategy:

• ACE inhibitors and calcium channel blockers are both first-line agents for hypertension 1
• Combinations of ACE inhibitors with CCBs are reasonable to achieve blood pressure targets 1
• The combination produces similar blood pressure lowering across all racial and ethnic groups 1
• Most patients with hypertension require two or more antihypertensive medications to achieve adequate blood pressure control 1

The 2007 ESH/ESC guidelines also list calcium antagonist plus ACE inhibitor as one of the preferred combinations in the general hypertensive population 1

When to Use This Combination

Start with combination therapy when:

• Initial blood pressure is grade 2 or 3 (≥160/100 mmHg) 1
• Total cardiovascular risk is high or very high 1
• Monotherapy with either agent fails to achieve target BP (<130/80 mmHg) after 4 weeks 4

Consider monotherapy first when:

• Blood pressure elevation is mild (stage 1: 130-139/80-89 mmHg) 4
• Total cardiovascular risk is low or moderate 1

Dosing Strategy

Start with lower doses in combination and titrate as needed:

• Initial: Amlodipine 2.5-5 mg + Lisinopril 5-10 mg once daily 2, 3
• If inadequate response after 2 weeks: Double lisinopril dose without changing amlodipine 5
• Maximum studied doses: Amlodipine 5 mg + Lisinopril 10 mg 2, 3

Special Population Considerations

Black patients: This combination is particularly appropriate because:

• Black patients respond less well to ACE inhibitor monotherapy 3
• However, they respond similarly to the combination as Caucasian patients 3
• The combination of ACE inhibitor with CCB produces similar blood pressure lowering in blacks as in other racial groups 1

Patients with high renin activity: The response to lisinopril correlates with baseline plasma renin activity, while amlodipine's effect is independent of renin levels 3

Patients with severe hypertension: Amlodipine response tends to be greater with higher initial blood pressure 3

If Combination Fails

When amlodipine plus lisinopril fails to control blood pressure, add a thiazide diuretic rather than a beta-blocker:

• Bendrofluazide 5 mg once daily causes significantly greater blood pressure reduction than atenolol 100 mg when added to amlodipine/lisinopril 6
• This creates a three-drug regimen consistent with guideline recommendations for resistant hypertension 1

Clinical Outcomes Beyond Blood Pressure

While the combination effectively lowers blood pressure, individual agent data shows:

• Amlodipine is as effective as chlorthalidone in preventing coronary heart disease mortality and more effective than lisinopril in reducing stroke events 1
• Lisinopril is less effective than amlodipine in preventing heart failure in the general population 1
• The combination provides organoprotective effects beyond blood pressure reduction 7, 5

Practical Implementation

Fixed-dose combination tablets simplify treatment and improve compliance 1, though individual titration may be needed initially 2, 5. Once stable, transition to fixed-dose combinations when available.

Monitor for:

• ACE inhibitor-related cough (more common in Asian Americans) 1
• Angioedema risk (higher in Black patients with ACE inhibitors) 1
• Peripheral edema from amlodipine (usually mild and dose-dependent)