Amlodipine is FDA approved for the treatment of hypertension and coronary artery disease (CAD).1 The Eighth Joint National Committee (JNC-8) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, deems amlodipine a first-line agent in the treatment of hypertension.2
Multiple studies have provided data to support the blood pressure lowering effects of amlodipine.3-8
In 2002, the large Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) evaluated the efficacy amlodipine, chlorthalidone, and lisinopril.9 The study included 33,357 patients over the age of 55 with at least one cardiovascular risk factor in addition to hypertension. The mean follow up was 4.9 years and a total of 9,048 individuals were randomized to the amlodipine group (receiving 2.5 mg, 5 mg, or 10 mg amlodipine per day). Among the individuals in the amlodipine group, systolic blood pressure decreased by an average of 11.5 mm Hg in the five years of the study and diastolic blood pressure decreased by an average of 9.3 mm Hg. Overall, 66.3% of people in the amlodipine arm achieved a blood pressure below 140/90.
A study that evaluated the use of amlodipine in patients with mild hypertension (diastolic blood pressure <100 mm Hg), found that amlodipine use led to a sizeable decrease in blood pressure (BP).3 Average systolic blood pressure decreased by 15.6 mm Hg and average diastolic blood pressure decreased by 12.9 mm Hg (p<0.01).
Julius et al. studied the efficacy of amlodipine in patients aged 50 years or older with treated or untreated hypertension and a high risk of cardiac events.6 Participants had a mean sitting systolic BP between 160-210 mm Hg, and a mean sitting diastolic BP less than 115 mm Hg. Participants at risk for cardiovascular disease with well-controlled BP were also included in the study in which a lower BP limit was not set. Treatment began with 5 mg of amlodipine and was titrated up in order to reach a target blood pressure of less than 140/90 mm Hg. Compared to baseline blood pressure, average BP among amlodipine users decreased by 17.3/9.9 mm Hg (p<0.0001).
A randomized, double-blind, placebo controlled study assessed the use of amlodipine among patients with mild to moderate hypertension (BP <180/110 mm Hg and diastolic BP ≥ 95 mm Hg).4 At the end of the eight-week study, amlodipine 2.5 mg, 5 mg, and 10 mg, decreased participants average BP by 12.4/9.3 mm Hg, 15.1/11.5 mm Hg, and 24.1/15.6 mm Hg, respectively.
According to practice guidelines, developed by the American College of Cardiology Foundation and the American Heart Association, calcium channel blockers are not recommended as routine treatment for patients with heart failure.10 However, amlodipine may be considered in the management of hypertension or ischemic heart disease in patients with heart failure.
Amlodipine is indicated to reduce the risk of hospitalization due to angina and to reduce the risk of a coronary revascularization procedure in patients with recently documented CAD by angiography and without heart failure or an ejection fraction <40%.5 Amlodipine is also specified for the symptomatic treatment of chronic stable angina as well as for the treatment of confirmed or suspected vasospastic angina.1
Treatment of vasospastic angina with amlodipine was evaluated in a randomized placebo controlled trail in which 24 patients received amlodipine and 28 received placebo.11 The rate of angina episodes during the four-week period decreased significantly among the amlodipine group (p=0.009). Twenty patients entered a one year open label protocol where the mean rate of angina episodes decreased from 1.6 episodes per day to 0.1 episodes per day (p=0.0094). Baseline intake of nitroglycerin also decreased from 1.3 tablets a week to 0.2 tablets a week.
The CAMELOT study of antihypertensive agents in patients with coronary disease and normal blood pressure found that amlodipine users had reduced rates of cardiovascular events.5 Cardiovascular events occurred in 16.6% of amlodipine treated patients compared to 23.1% of placebo treated patients (hazard ratio [HR], 0.69; 95% CI, 0.54-0.88 [p=0.003]). Average blood pressure decreased by 4.8/2.5 mmHg in the amlodipine group whereas the average blood pressure in the placebo group increased by 0.7/0.6 mm Hg. Atherosclerosis progression was measured by intravascular ultrasound in a sub-study of 274 patients randomized to amlodipine, placebo, or enalapril. Compared to baseline, both placebo (p<0.001) and enalapril (p=0.08) groups had atherosclerosis progression. There was no progression of atherosclerosis in the amlodipine group (p=0.31).
References
- Amlodipine Besylate. Drugs@FDA. https://www.accessdata.fda.gov/. Accessed May 10, 2017.
- James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). Jama. 2014;311(5):507-520.
- Neaton JD, Grimm RH, Prineas RJ, et al. Treatment of mild hypertension study: final results. Jama. 1993;270(6):713-724.
- Philipp T, Smith TR, Glazer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension. Clinical Therapeutics. 2007/04/01 2007;29(4):563-580.
- Nissen SE, Tuzcu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. Jama. Nov 10 2004;292(18):2217-2225.
- Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. The Lancet. 6/19/ 2004;363(9426):2022-2031.
- Webster J, Robb OJ, Jeffers TA, Scott AK, Petrie JC. Once-Daily Amlodipine in the Treatment of Mild to Moderate Hypertension. Journal of Cardiovascular Pharmacology. 1988;12:S72&hyhen;S75.
- Abernethy DR, Gutkowska J, Winterbottom LM. Effects of amlodipine, a long‐acting dihydropyridine calcium antagonist in aging hypertension: pharmacodynamics in relation to disposition. Clinical Pharmacology & Therapeutics. 1990;48(1):76-86.
- Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Jama. Dec 18 2002;288(23):2981-2997.
- Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013.
- Chahine RA, Feldman RL, Giles TD, et al. Randomized placebo-controlled trial of amlodipine in vasospastic angina. Journal of the American College of Cardiology. 1993;21(6):1365-1370.
