What is the effect of Amlodipine (Calcium Channel Blocker)?

From the Guidelines

Amlodipine, a calcium channel blocker, is effective in treating high blood pressure and certain types of chest pain, but its use should be carefully considered due to potential limitations and side effects, as evidenced by recent guidelines 1. The primary mechanism of action of amlodipine is to relax and widen blood vessels, allowing blood to flow more easily and reducing the workload on the heart.

• The typical starting dose is 5 mg once daily, which may be increased to a maximum of 10 mg daily if needed for blood pressure control.
• Amlodipine should be taken at the same time each day, with or without food, and requires consistent daily use to be effective.
• Common side effects include swelling in the ankles or feet, headache, flushing, and dizziness, which often diminish over time as the body adjusts to the medication. According to the 2022 AHA/ACC/HFSA guideline for the management of heart failure, dihydropyridine calcium channel blockers like amlodipine may be used for treating hypertension in patients with elevated blood pressure despite optimization of guideline-directed medical therapy (GDMT) 1.
• However, the PRAISE-1 and PRAISE-2 trials showed mixed results regarding the survival benefit of amlodipine in patients with nonischemic cardiomyopathy, highlighting the need for careful patient selection and monitoring 1. In contrast to older studies, such as the ALLHAT trial, which compared the effectiveness of an ACE inhibitor, a calcium-channel blocker, and a thiazide diuretic as first-line therapy for mild to moderate hypertension 1, more recent guidelines prioritize the use of ACE inhibitors or ARBs as first-line agents for patients with heart failure or diabetes.
• The ALLHAT trial found no differences between treatments in primary outcome or all-cause mortality, but the amlodipine group had a higher risk for heart failure than the chlorthalidone group 1. Overall, the decision to use amlodipine should be based on individual patient characteristics, comorbidities, and response to treatment, with careful consideration of potential benefits and risks, as well as alternative treatment options 1.

From the FDA Drug Label

Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure Following administration of therapeutic doses to patients with hypertension, amlodipine produces vasodilation resulting in a reduction of supine and standing blood pressures.

The effect of Amlodipine is to:

• Reduce peripheral vascular resistance
• Lower blood pressure by acting as a peripheral arterial vasodilator
• Relieve angina by reducing myocardial oxygen demand and inhibiting coronary spasm 2

From the Research

Effects of Amlodipine on Cardiovascular Health

• Amlodipine has been shown to significantly reduce weekly anginal attacks and consumption of glyceryl trinitrate tablets in patients with stable exertional angina pectoris and mild-to-moderate hypertension 3.
• The drug has also been found to improve exercise tolerance, increasing total exercise time, exercise time to angina onset, and time to ST segment depression, while decreasing ST segment depression and the duration of pain 3, 4.
• Amlodipine has been demonstrated to lower blood pressure in patients with hypertension, with a significant reduction in systolic blood pressure observed in one study 4.
• The drug has also been shown to reduce the number of angina attacks and nitroglycerin consumption, and to produce a sustained improvement in exercise performance in patients with severe coronary artery disease 4.

Comparison with Other Calcium Channel Blockers

• Amlodipine has been compared to other calcium channel blockers, such as nifedipine and diltiazem, in terms of its efficacy and tolerability in patients with vasospastic angina 5.
• While all three drugs were found to be effective in decreasing vasospastic angina, amlodipine was found to decrease it by 17%±140% and 33% after 6 weeks, although further studies are needed to confirm this finding 5.
• Amlodipine has also been compared to nifedipine in terms of its antianginal and hypotensive efficacy, with amlodipine found to have markedly better anti-anginal efficacy than nifedipine with respect to most of the parameters examined 3.

Long-term Effects and Safety

• The long-term efficacy and safety of amlodipine have been assessed in several studies, with one study finding that the drug resulted in a significant reduction in angina attack rate and nitroglycerin consumption, which was maintained during follow-up 4.
• Amlodipine has also been found to be well tolerated, with no serious adverse events occurring in any patients during therapy with the drug 3, 6.
• However, the drug has been associated with vasodilator adverse events, such as oedema, headaches, and flushing, although these are commonly observed with other calcium channel blockers as well 6.