What is the association between Norvasc (Amlodipine) and chronic systolic heart failure (CHF)?

From the Guidelines

Norvasc (amlodipine) should generally be avoided in patients with chronic systolic congestive heart failure (CHF) unless needed for other compelling indications like hypertension or angina. Amlodipine is a dihydropyridine calcium channel blocker that causes peripheral vasodilation, which can initially worsen heart failure symptoms by activating neurohormonal compensatory mechanisms 1. Unlike other calcium channel blockers such as verapamil or diltiazem that have negative inotropic effects, amlodipine has minimal direct negative impact on cardiac contractility. If amlodipine must be used in a patient with systolic heart failure, it should be initiated at a low dose (2.5 mg daily) and carefully titrated while monitoring for signs of worsening heart failure such as increased edema, shortness of breath, or weight gain. Some key points to consider when using amlodipine in patients with CHF include:

• The potential for amlodipine to worsen heart failure symptoms due to its vasodilatory effects 1
• The importance of careful titration and monitoring when initiating amlodipine in patients with CHF
• The availability of alternative treatments for hypertension and angina that may be more suitable for patients with CHF First-line medications for chronic systolic heart failure include ACE inhibitors or ARBs, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, as these medications have demonstrated mortality benefits 1. The physiological concern with amlodipine in heart failure is that the vasodilation it causes can trigger compensatory mechanisms including activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, potentially worsening the underlying pathophysiology of heart failure. Key considerations for the use of amlodipine in CHF patients include:
• The need for careful patient selection and monitoring
• The importance of optimizing guideline-directed medical therapy (GDMT) for CHF before considering the use of amlodipine
• The potential for amlodipine to interact with other medications commonly used in CHF patients, such as beta-blockers and ACE inhibitors.

From the FDA Drug Label

Amlodipine has been compared to placebo in four 8 to 12 week studies of patients with NYHA Class II/III heart failure, involving a total of 697 patients. In these studies, there was no evidence of worsened heart failure based on measures of exercise tolerance, NYHA classification, symptoms, or left ventricular ejection fraction. In a long-term (follow-up at least 6 months, mean 13. 8 months) placebo-controlled mortality/morbidity study of amlodipine 5 to 10 mg in 1153 patients with NYHA Classes III (n=931) or IV (n=222) heart failure on stable doses of diuretics, digoxin, and ACE inhibitors, amlodipine had no effect on the primary endpoint of the study which was the combined endpoint of all-cause mortality and cardiac morbidity (as defined by life-threatening arrhythmia, acute myocardial infarction, or hospitalization for worsened heart failure), or on NYHA classification, or symptoms of heart failure.

The association between Norvasc (amlodipine) and chronic systolic CHF suggests that amlodipine does not worsen heart failure in patients with NYHA Class II/III heart failure. Key points include:

• No evidence of worsened heart failure based on measures of exercise tolerance, NYHA classification, symptoms, or left ventricular ejection fraction.
• No effect on the primary endpoint of all-cause mortality and cardiac morbidity in a long-term study.
• No significant difference in NYHA classification or symptoms of heart failure. However, pulmonary edema was reported more frequently with amlodipine in one study 2.

From the Research

Association between Norvasc and Chronic Systolic CHF

• The association between Norvasc (amlodipine) and chronic systolic congestive heart failure (CHF) has been studied in several trials 3, 4, 5.
• Amlodipine, a long-acting dihydropyridine derivative, has been shown to be safe and potentially beneficial in patients with heart failure due to coronary artery disease 3.
• The PRAISE study demonstrated a substantial reduction in mortality in patients with CHF due to nonischemic cardiomyopathy, providing a strong indication for a potential therapeutic benefit of amlodipine when added to standard CHF therapy in this patient population 3.
• However, other calcium channel blockers have been shown to have a detrimental effect in some patients with CHF, and therefore, cannot be considered safe for use in patients with moderate-to-severe heart failure 3, 6.
• The use of amlodipine in combination with angiotensin-converting enzyme (ACE) inhibition has been shown to provide beneficial effects in a model of CHF, with improved left ventricular function, hemodynamics, and neurohormonal system activity 5.

Safety and Efficacy of Amlodipine in CHF

• Amlodipine has been shown to be well-tolerated and effective in patients with CHF, with a favorable effect on exercise tolerance and mortality 3, 5.
• However, the use of other calcium channel blockers in CHF is generally not recommended, except in special situations, due to the potential for detrimental effects 4, 6.
• The safety and efficacy of amlodipine in CHF have been demonstrated in several studies, including the PRAISE study, which showed a substantial reduction in mortality in patients with CHF due to nonischemic cardiomyopathy 3.