Can Amlodipine and Lisinopril be used together to treat hypertension?

Amlodipine and Lisinopril Combination Therapy for Hypertension

Yes, amlodipine and lisinopril can and should be used together for hypertension management—this combination is explicitly recommended by ACC/AHA guidelines as a rational, complementary pairing that produces additive blood pressure lowering effects. 1, 2

Guideline-Based Rationale for Combination

The 2017 ACC/AHA guidelines specifically endorse combining ACE inhibitors (like lisinopril) with calcium channel blockers (like amlodipine) because they have complementary mechanisms of action. 1 Thiazide diuretics may stimulate the renin-angiotensin-aldosterone system, and adding an ACE inhibitor blocks this compensatory response, resulting in additive BP lowering. 1 The same principle applies when combining CCBs with ACE inhibitors—each targets different pathways controlling blood pressure. 2

Both amlodipine and lisinopril are designated as first-line agents for hypertension treatment. 1, 3, 4 The European Society of Hypertension/ESC guidelines list calcium antagonist plus ACE inhibitor as one of the preferred combinations in the general hypertensive population. 2

When to Use Combination Therapy

Initiate combination therapy with two first-line agents when:

• Stage 2 hypertension is present (BP ≥140/90 mmHg or more than 20/10 mmHg above target) 1
• Initial BP is grade 2 or 3 (≥160/100 mmHg) 2
• Total cardiovascular risk is high or very high 2

Start with monotherapy when:

• Stage 1 hypertension (130-139/80-89 mmHg) with low to moderate cardiovascular risk 1, 2
• Then add the second agent if target BP <130/80 mmHg is not achieved 1

Clinical Evidence of Efficacy

Research demonstrates that the amlodipine-lisinopril combination produces significantly greater BP reduction than either agent alone. 5 In a randomized crossover study, the combination of just 2.5 mg amlodipine with 5 mg lisinopril produced more significant BP lowering in a higher percentage of patients than individual low doses. 5

A 12-week trial showed that low-dose combined treatment with amlodipine and lisinopril achieved target BP in more patients and produced greater systolic and diastolic BP reductions than monotherapy with either drug alone. 6 Both drugs together were well-tolerated and efficacious in patients with stage 2 hypertension, with response rates approaching 100%. 7

Special Population Considerations

For Black patients: This combination is particularly appropriate because ACE inhibitors like lisinopril are less effective as monotherapy in Black patients compared to CCBs or thiazides. 1, 4 However, the combination of ACE inhibitor with CCB produces similar BP lowering in Black patients as in other racial groups. 2 The ALLHAT trial showed that in Black patients, ACE inhibitors were notably less effective than CCBs in preventing heart failure and stroke. 1

For patients with diabetes: Both agents are appropriate, though specific comorbidities (like diabetic nephropathy) may favor ACE inhibitors. 1

For patients with heart failure: Amlodipine can be used as a step 3 agent in heart failure patients with persistent hypertension despite treatment with ACE inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. 8

Practical Implementation

Dosing strategy:

• Start with amlodipine 2.5-5 mg plus lisinopril 5-10 mg once daily 5, 6
• Titrate upward if needed: amlodipine up to 10 mg, lisinopril up to 40 mg 3, 4
• Fixed-dose combination tablets are available and can improve compliance 2

Monitoring requirements:

• Check basic metabolic panel for renal function and potassium, especially with lisinopril 4
• Monitor for ACE inhibitor-related cough (occurs in some patients) 2
• Watch for angioedema risk, particularly in Black patients and Asian Americans 2
• Assess BP response within 1-2 weeks 9

When Combination Fails

If BP remains uncontrolled on amlodipine plus lisinopril, add a thiazide diuretic rather than a beta-blocker. 10 A randomized crossover study demonstrated that in patients not adequately controlled on amlodipine 5 mg and lisinopril 10 mg daily, adding bendroflumethiazide 5 mg caused a significantly greater fall in BP compared to adding atenolol 100 mg. 10

Critical Contraindications

Never combine lisinopril with:

• Another ACE inhibitor 1
• An ARB (angiotensin receptor blocker) 1
• Direct renin inhibitor aliskiren 1

High-quality RCT data demonstrate that simultaneous administration of RAS blockers increases cardiovascular and renal risk. 1

Mechanism and Pharmacology

Lisinopril inhibits ACE, reducing angiotensin II and aldosterone, leading to vasodilation and decreased sodium retention. 4 Amlodipine blocks calcium channels in vascular smooth muscle, causing direct vasodilation. 3 These complementary mechanisms explain the additive effect when combined. 1, 2

The combination addresses multiple pathways: lisinopril suppresses the renin-angiotensin-aldosterone system while amlodipine provides direct vasodilation independent of this system. 4 This is particularly valuable since many patients require more than one drug to achieve BP goals. 3

Cost-Effectiveness

Low-dose combined treatment with lisinopril and amlodipine is more cost-efficient than higher-dose monotherapy with either agent. 6 Additionally, lisinopril may correct some CNS side effects associated with amlodipine monotherapy. 6