In an adult with essential hypertension and no contraindications, should I initiate amlodipine or lercanidipine as first‑line therapy?

Amlodipine vs Lercanidipine for Essential Hypertension

For an adult with essential hypertension and no contraindications, initiate amlodipine rather than lercanidipine as first-line therapy. Amlodipine is explicitly recommended by major international guidelines as a first-line agent, while lercanidipine lacks guideline endorsement and is not available in the United States. 1, 2

Guideline-Based Recommendations

First-Line Drug Classes

• The WHO, ACC/AHA, and ESC guidelines uniformly recommend long-acting dihydropyridine calcium channel blockers as first-line therapy for essential hypertension, alongside thiazide diuretics, ACE inhibitors, and ARBs. 1, 2

• Amlodipine is the prototypical long-acting dihydropyridine CCB studied extensively in major cardiovascular outcome trials and specifically mentioned in treatment algorithms. 1

• Lercanidipine is not mentioned in any major hypertension guideline (ACC/AHA 2017, WHO 2022, ESC) as a recommended agent, despite being available in some countries outside the United States. 1, 2

Treatment Initiation Strategy

• For most patients with confirmed hypertension ≥140/90 mmHg, guidelines recommend starting with combination therapy using two drugs from different classes, preferably as a single-pill combination. 2

• If initiating monotherapy, amlodipine 5-10 mg once daily is appropriate, with dose titration based on response. 1

• Monthly follow-up is recommended after initiating therapy until blood pressure targets are achieved (<130/80 mmHg for high-risk patients, <140/90 mmHg for others). 1, 2

Comparative Evidence Between Agents

Efficacy Profile

• Lercanidipine 10-20 mg daily demonstrates equivalent blood pressure reduction compared to amlodipine 10 mg daily in head-to-head trials of mild-to-moderate hypertension over 2-16 weeks. 3, 4

• Both agents achieve response rates (DBP <90 mmHg) of 50-86% depending on dose and patient population. 3, 5

• Lercanidipine has a slower onset and longer duration of action due to high lipophilicity and membrane-controlled kinetics, which theoretically reduces reflex tachycardia. 3, 6

Tolerability Considerations

• The most clinically relevant difference is peripheral edema incidence: lercanidipine appears to cause significantly less ankle edema than amlodipine or nifedipine GITS in comparative studies. 7, 3, 5

• Common adverse effects for both agents include headache, flushing, and dizziness, typical of all dihydropyridine calcium channel blockers. 3, 4

• Neither agent causes significant heart rate changes, an advantage over short-acting dihydropyridines. 4, 6

Clinical Decision Algorithm

When to Choose Amlodipine (Preferred)

• Use amlodipine as the default first-line dihydropyridine CCB because it is guideline-recommended, widely available, has extensive outcome data, and is available in fixed-dose combinations with ACE inhibitors, ARBs, and thiazides. 1, 2

• Amlodipine is specifically recommended for patients with stable ischemic heart disease and angina when added to beta-blockers for persistent hypertension. 1

• Amlodipine combined with ACE inhibitors or ARBs reduces cardiovascular events in high-risk populations, supported by major outcome trials like ALLHAT and ACCOMPLISH. 1

When Lercanidipine Might Be Considered (If Available)

• Consider lercanidipine only if amlodipine causes intolerable peripheral edema and the drug is available in your region, as it has a lower edema incidence. 7, 3, 5

• Lercanidipine may be appropriate for elderly patients with isolated systolic hypertension where edema risk is particularly problematic, though amlodipine remains guideline-preferred. 3, 4

• Lercanidipine is not available in the United States, limiting its practical utility for most North American practitioners. 7

Important Caveats

Contraindications to Consider

• Avoid all dihydropyridine CCBs in patients with heart failure with reduced ejection fraction (HFrEF) unless specifically needed for angina or uncontrolled hypertension after GDMT, as they lack mortality benefit and may worsen outcomes. 1

• Non-dihydropyridine CCBs (verapamil, diltiazem) are absolutely contraindicated in HFrEF due to negative inotropic effects. 1

Combination Therapy Considerations

• If blood pressure remains uncontrolled on amlodipine monotherapy after 4 weeks, escalate to dual or triple therapy rather than switching to lercanidipine, as the issue is inadequate blood pressure reduction, not drug selection. 2, 8

• Preferred combinations include amlodipine + ACE inhibitor/ARB + thiazide diuretic, available as single-pill combinations to improve adherence. 1, 2, 8

Monitoring Requirements

• Check serum creatinine, electrolytes, and fasting glucose before initiating any antihypertensive therapy, though testing should not delay treatment initiation. 1, 2

• Reassess blood pressure monthly until target is achieved, then every 3-5 months once controlled. 1, 2