Reviewed by MedNext Clinical Team
Amlodipine is a dihydropyridine calcium channel blocker (CCB) and one of the most frequently prescribed antihypertensive agents globally. Its once-daily dosing, long half-life, well-characterised cardiovascular outcome data, and favourable tolerability profile have secured its position as a first-line option for hypertension and stable angina in multiple international guidelines [1].
Mechanism of Action
Amlodipine blocks voltage-gated L-type calcium channels in vascular smooth muscle cells and cardiac myocytes. Inhibition of calcium influx in peripheral arterial smooth muscle causes vasodilation and reduction in systemic vascular resistance, lowering blood pressure. Its very slow receptor-binding kinetics and long plasma half-life (35–50 hours) produce gradual, sustained blood pressure reduction without the reflex tachycardia seen with shorter-acting dihydropyridines.
Indications
Amlodipine is indicated for hypertension (as monotherapy or in combination) and for the prophylaxis of stable angina. It is particularly preferred in: patients of African or Afro-Caribbean origin (where CCBs and diuretics are more effective than ACE inhibitors or beta-blockers as first-line agents); isolated systolic hypertension in the elderly; patients with co-existing angina; and patients in whom ACE inhibitors or ARBs are contraindicated or poorly tolerated. It is safe to use in patients with asthma and in those with left ventricular dysfunction, unlike some other antihypertensive classes [1].
Cardiovascular Outcome Evidence
The ALLHAT trial — one of the largest antihypertensive outcome trials ever conducted, involving over 33,000 participants — demonstrated that amlodipine was non-inferior to chlorthalidone (thiazide-type diuretic) for the primary composite outcome of fatal coronary heart disease and non-fatal myocardial infarction, and superior for prevention of stroke and heart failure endpoints in specific subgroups [1]. Amlodipine was superior to lisinopril for stroke prevention, particularly in Black patients. The ASCOT-BPLA trial further demonstrated the superiority of amlodipine-based therapy over atenolol-based therapy for cardiovascular outcomes.
Dosing
The standard adult dose is 5 mg once daily, increased to 10 mg once daily if blood pressure target is not achieved at 4 weeks. In elderly patients (aged 65 and over) and in those with hepatic impairment, initiation at 2.5 mg once daily reduces the risk of hypotension. The long half-life means that missed doses have less clinical impact than with shorter-acting agents, supporting adherence.
Ankle Oedema
Peripheral ankle oedema is the most common clinically significant adverse effect of amlodipine, occurring in approximately 10–15% of patients and more commonly in women and at higher doses. It results from precapillary arteriolar vasodilation without equivalent venular dilation, increasing hydrostatic pressure and causing fluid transudation into the interstitium. It is not a manifestation of fluid retention and does not respond to diuretics. If problematic, switching to an ARB or combining amlodipine with an ACE inhibitor or ARB can substantially reduce oedema through venodilation [1].
Combination Therapy
Amlodipine is commonly combined with an ACE inhibitor (e.g. ramipril) or ARB (e.g. losartan) as a highly effective dual antihypertensive combination, recommended in national hypertension guidelines. The addition of a thiazide-like diuretic as a third agent achieves blood pressure targets in the majority of patients not controlled on dual therapy. Fixed-dose combination formulations of amlodipine with a renin-angiotensin system blocker improve adherence and are preferred in patients requiring combination therapy.
References
- ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic. JAMA. 2002;288(23):2981-2997.