Which calcium channel blockers (CCBs) are safe in heart failure with reduced ejection fraction (HFrEF)?

Calcium Channel Blockers in Heart Failure with Reduced Ejection Fraction

Direct Answer

No calcium channel blockers are recommended for the treatment of HFrEF itself, but amlodipine may be used cautiously when needed for comorbid hypertension or angina that persists despite optimal guideline-directed medical therapy. 1

Evidence-Based Recommendations by CCB Class

Non-Dihydropyridine CCBs (Diltiazem, Verapamil)

• These agents are contraindicated and cause harm in HFrEF patients (Class of Recommendation 3: Harm, Level of Evidence A). 1
• Non-dihydropyridines possess significant negative inotropic effects and myocardial depressant activity that worsen heart failure outcomes. 1
• They should be completely avoided in all HFrEF patients regardless of comorbidities. 1, 2

Dihydropyridine CCBs (Except Amlodipine)

• Dihydropyridine CCBs are not recommended for HF treatment (Class of Recommendation 3: No Benefit, Level of Evidence A). 1
• Agents like felodipine and other first-generation dihydropyridines showed no mortality benefit in clinical trials despite theoretical afterload reduction benefits. 1
• These medications provide no therapeutic value for heart failure management itself. 1

Amlodipine - The Exception

Amlodipine is the only CCB that may be safely used in HFrEF patients when clinically indicated for other conditions. 1

Safety Profile

• Amlodipine demonstrated neutral effects on mortality and morbidity in the PRAISE-1 trial, with no increased risk of worsening heart failure. 1, 3, 4
• The drug showed no significant excess of adverse events (10% worsening HF with amlodipine vs 6.3% with placebo, not statistically significant). 5
• Long-term studies in 1,153 patients with NYHA Class III/IV heart failure showed no detrimental effect on the combined endpoint of all-cause mortality and cardiac morbidity. 3, 4

When to Use Amlodipine

• For hypertension: May be added when blood pressure remains elevated despite optimization of guideline-directed medical therapy (ACE inhibitors/ARBs, beta-blockers, mineralocorticoid receptor antagonists). 1
• For angina: Can be used for management of ischemic symptoms in HFrEF patients with coronary artery disease. 1, 3
• The typical dose is 5-10 mg once daily. 3, 5

Important Caveats About Amlodipine

• While the PRAISE-1 trial suggested mortality benefit in the nonischemic cardiomyopathy subgroup, the PRAISE-2 trial failed to confirm this benefit when specifically studying only nonischemic patients, demonstrating the unreliability of subgroup analyses. 1
• Amlodipine provides no additional benefit for heart failure treatment itself - it showed no improvement in exercise tolerance, quality of life, or NYHA functional class compared to placebo. 5
• The drug improved ejection fraction by 3.4% vs 1.5% with placebo (p=0.007), but this did not translate to clinical benefit. 5

Clinical Algorithm for CCB Use in HFrEF

1. First, optimize guideline-directed medical therapy: Ensure patients are on appropriate doses of ACE inhibitors/ARBs/ARNI, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors before considering any CCB. 2

2. Assess the indication:

   • If CCB is being considered for heart failure treatment → Do not prescribe any CCB. 1
   • If CCB is needed for persistent hypertension despite optimal HF therapy → Consider amlodipine only. 1
   • If CCB is needed for angina despite optimal HF therapy → Consider amlodipine only. 1

3. Verify CCB type:

   • Non-dihydropyridine (diltiazem, verapamil) → Discontinue immediately - these cause harm. 1
   • Dihydropyridine other than amlodipine → Switch to amlodipine if CCB is truly needed for comorbidity. 1
   • Amlodipine → May continue if indicated for hypertension or angina. 1

4. Monitor for adverse effects:

   • Watch for signs of worsening heart failure (increased dyspnea, edema, weight gain). 3
   • Monitor for pulmonary edema, which occurred more frequently with amlodipine in some trials. 3
   • Assess for peripheral edema, a common side effect that may be confused with HF decompensation. 3

Common Pitfalls to Avoid

• Do not use CCBs for rate control in atrial fibrillation with HFrEF: One study found 7.3% of HFrEF patients with atrial fibrillation were inappropriately discharged on contraindicated CCBs, with 86.7% receiving multiple AV nodal blockers. 6 Use beta-blockers or digoxin instead for rate control.

• Do not assume all dihydropyridines are equivalent: Only amlodipine has been adequately studied for safety in HFrEF; other dihydropyridines like nicardipine and nisoldipine have shown detrimental effects. 7

• Do not prescribe CCBs based on theoretical hemodynamic benefits: Despite favorable afterload reduction, CCBs consistently fail to improve functional capacity or survival in HFrEF. 1, 5

• Avoid polypharmacy with multiple AV nodal blockers: If amlodipine is used, ensure coordination with other rate-controlling medications to prevent excessive bradycardia. 6