For hypertension, which dihydropyridine calcium‑channel blocker—amlodipine, cilnidipine, or nifedipine—is the most appropriate first‑line choice?

Amlodipine vs Cilnidipine vs Nifedipine for Hypertension

Amlodipine is the most appropriate first-line dihydropyridine calcium channel blocker for hypertension, with proven cardiovascular risk reduction, 24-hour blood pressure control with once-daily dosing, and explicit guideline endorsement. 1

Guideline-Supported First-Line Choice

• The American College of Cardiology and American Heart Association explicitly recommend long-acting dihydropyridine calcium channel blockers like amlodipine as appropriate initial therapy for hypertension, with proven cardiovascular risk reduction and effective 24-hour blood pressure control. 1

• The landmark ALLHAT study definitively established that amlodipine was equally effective as thiazide diuretics in preventing coronary heart disease mortality and nonfatal myocardial infarction, with consistent results across all patient subgroups including elderly, diabetic, and Black patients. 1

• Cilnidipine is not mentioned in any major U.S. or international hypertension guidelines and lacks FDA approval, limiting its use to select markets outside the United States. 1

• Immediate-release nifedipine should never be used for chronic hypertension management due to reflex tachycardia and potential worsening of myocardial ischemia, and is explicitly contraindicated in acute coronary syndromes without beta-blocker therapy. 2

Clinical Decision Algorithm

For Uncomplicated Hypertension:

• Start amlodipine 5 mg once daily, titrate to 10 mg after 4 weeks if blood pressure target (<130/80 mmHg) is not achieved. 1
• If monotherapy is insufficient, add an ACE inhibitor, ARB, or thiazide diuretic as second-line therapy. 1

For Black Patients Without Comorbidities:

• Calcium channel blockers like amlodipine are more effective than ACE inhibitors in preventing heart failure and stroke in this population. 1

For Patients with Specific Comorbidities:

• For established coronary artery disease or albuminuria ≥300 mg/g creatinine, initiate ACE inhibitor or ARB first, then add amlodipine if blood pressure remains uncontrolled. 2, 1
• For heart failure with reduced ejection fraction, avoid amlodipine as first-line therapy; use only after ACE inhibitors/ARBs, beta-blockers, and diuretics if blood pressure control is still needed. 1, 3

Comparative Evidence on Cilnidipine

While cilnidipine blocks both L-type and N-type calcium channels (versus amlodipine's L-type only blockade), the clinical significance is limited:

• Small studies suggest cilnidipine may reduce urinary albumin excretion and improve arterial stiffness more than amlodipine in diabetic hypertensive patients. 4, 5
• However, these studies involved only 50-77 patients and lack the robust cardiovascular outcome data that established amlodipine's safety and efficacy in the ALLHAT trial of over 33,000 patients. 1
• The theoretical sympatholytic advantage of N-type calcium channel blockade has not translated into superior cardiovascular outcomes in large-scale trials. 4, 5

Comparative Evidence on Nifedipine

• Short-acting nifedipine is explicitly contraindicated due to dose-related increases in mortality in patients with coronary artery disease and harm in acute coronary syndromes. 2
• Even slow-release nifedipine formulations require twice-daily dosing and show significant peak/trough blood pressure variability compared to amlodipine's stable 24-hour control. 6
• Amlodipine demonstrates better tolerability with lower incidence of side effects (dizziness, headache, flushing) compared to nifedipine formulations. 3, 7

Critical Monitoring and Pitfalls

• Assess for dose-related peripheral edema with amlodipine, which occurs more frequently at 10 mg dosing; consider dose reduction if bothersome. 1, 3
• Monitor for orthostatic hypotension when initiating amlodipine, particularly in elderly patients or those on multiple antihypertensive agents. 3
• Never combine amlodipine with short-acting nifedipine or use short-acting nifedipine for any chronic hypertension management. 2
• Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in patients with heart failure due to negative inotropic effects. 2, 3