Can calcium channel blockers (CCBs) be used in patients with heart failure?

Calcium Channel Blockers in Heart Failure: Use Depends on Heart Failure Type and CCB Subclass

Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) are contraindicated in heart failure with reduced ejection fraction (HFrEF) due to their negative inotropic effects, while second-generation dihydropyridines like amlodipine have neutral mortality effects and may be used when needed for hypertension or angina. 1, 2

Heart Failure with Reduced Ejection Fraction (HFrEF)

Non-Dihydropyridine CCBs: Contraindicated

• Verapamil and diltiazem are Class III (Harm) recommendations in HFrEF due to their myocardial depressant effects and negative inotropic activity 1
• These agents directly depress left ventricular contractility and can precipitate acute decompensation 1, 2
• Diltiazem was associated with higher risk of recurrent heart failure in post-MI patients with reduced ejection fraction 1
• Verapamil showed no survival benefit and potential harm in HFrEF patients 1

First-Generation Dihydropyridines: Not Recommended

• Short-acting nifedipine and similar agents should be avoided as they can worsen heart failure and increase cardiovascular events 2
• These lack the vascular selectivity of newer agents 3

Second-Generation Dihydropyridines: Safe When Necessary

• Amlodipine and felodipine have neutral effects on mortality and may be used for concurrent hypertension or angina 1, 2
• The PRAISE-1 trial initially suggested mortality benefit in nonischemic cardiomyopathy, but PRAISE-2 (enrolling only nonischemic patients) showed no survival benefit 1
• Amlodipine was well-tolerated in long-term studies of 1,153 patients with NYHA Class III/IV heart failure, showing no effect on the combined endpoint of all-cause mortality and cardiac morbidity 4
• If a CCB must be used in HFrEF, amlodipine is the only acceptable choice 2

Clinical Algorithm for HFrEF Patients Requiring Blood Pressure Control

1. First-line: ACE inhibitors/ARBs and beta-blockers (proven mortality benefit) 2
2. Second-line: Add diuretics or hydralazine/nitrates 2
3. Third-line: Consider amlodipine only if refractory hypertension or angina persists despite optimal guideline-directed medical therapy 2

Heart Failure with Preserved Ejection Fraction (HFpEF)

Rate-Limiting CCBs May Be Beneficial

• Verapamil may improve exercise capacity and symptoms in HFpEF patients based on two small studies (<30 patients each) 1
• Rate-limiting CCBs (verapamil, diltiazem) can be useful for ventricular rate control in atrial fibrillation, treatment of hypertension, and myocardial ischemia in HFpEF 1
• This represents a key exception: CCBs that are dangerous in HFrEF may be beneficial in HFpEF due to improved diastolic function and ventricular relaxation 1, 2
• Recent pooled analysis of 16,954 patients with HFmrEF/HFpEF showed CCB use was associated with lower pump failure death (HR 0.76) without increased risk of death or HF hospitalization 5

Critical Pitfalls to Avoid

Common Prescribing Errors

• 7.3% of patients with HFrEF and atrial fibrillation are inappropriately discharged on contraindicated CCBs (non-amlodipine agents), with no improvement in this rate over time 6
• 86.7% of these patients were on multiple AV nodal blocking agents, indicating lack of coordination between prescribers 6
• Female sex (OR 3.01) and hypertension (OR 7.87) were associated with inappropriate CCB prescription 6

Specific Contraindications in Aortic Stenosis

• CCBs should be avoided in patients with aortic stenosis and hypertension when possible 1
• In a retrospective study of 314 patients with moderate-severe aortic stenosis, CCB use was associated with sevenfold increase in mortality 1

Drug Interactions and Monitoring

• CCBs should be discontinued or dose-reduced when managing symptomatic hypotension in heart failure patients 1
• Avoid combining CCBs with other vasodilators (nitrates) unless absolutely necessary 1
• Non-dihydropyridine CCBs should be avoided in patients with heart failure with reduced ejection fraction even when combined with other medications 7

Summary by CCB Type and Heart Failure Classification

HFrEF (EF <40%):

• Non-dihydropyridines: Contraindicated 1, 2
• First-generation dihydropyridines: Not recommended 2
• Amlodipine/felodipine: Safe when needed for hypertension/angina 1, 2, 4

HFpEF (EF ≥50%):

• All CCB classes: May be used, potentially beneficial 1, 5
• Rate-limiting CCBs particularly useful for rate control and diastolic dysfunction 1