What are the contraindications of Calcium Channel Blockers (CCBs)?

Contraindications of Calcium Channel Blockers

Calcium channel blockers are absolutely contraindicated in patients with severe left ventricular dysfunction, second- or third-degree atrioventricular block without a pacemaker, sick sinus syndrome, and immediate-release nifedipine should never be used without concurrent beta-blocker therapy. 1

Absolute Contraindications by Drug Class

Non-Dihydropyridines (Verapamil, Diltiazem)

Cardiac Conduction Abnormalities:

• Second- or third-degree AV block without a cardiac pacemaker 1
• PR interval greater than 0.24 seconds 1
• Sick sinus syndrome (verapamil may interfere with sinus-node impulse generation and induce sinus arrest or sinoatrial block) 2, 3

Cardiac Dysfunction:

• Clinically significant left ventricular dysfunction 1
• Increased risk for cardiogenic shock 1
• Severe heart failure or pulmonary edema (verapamil and diltiazem can cause abrupt decompensation) 1, 4, 5
• Decompensated heart failure 1

Arrhythmia-Related:

• Pre-excitation syndromes (contraindication for non-dihydropyridines due to risk of accelerated ventricular rate) 6
• Atrial flutter or atrial fibrillation with accessory AV pathway (risk of ventricular fibrillation) 2

Dihydropyridines (Nifedipine, Amlodipine)

Immediate-Release Nifedipine Specific:

• Absence of concurrent beta-blocker therapy (Class III: Harm recommendation) 1
• Acute coronary syndromes without beta-blockade (causes dose-related increase in mortality) 1

All Dihydropyridines:

• Vasospastic conditions when beta-blockers are contraindicated (beta-blockers are contraindicated in vasospastic angina as they precipitate spasm) 1

Relative Contraindications and High-Risk Situations

Heart Failure with Reduced Ejection Fraction (HFrEF)

Most CCBs except amlodipine are not recommended in HFrEF:

• Any CCB other than amlodipine should be avoided in patients with LVEF <0.40 7, 8
• Verapamil causes the greatest negative inotropic effect, followed by diltiazem, then nifedipine 3, 5
• Verapamil can result in abrupt decompensation with overt pulmonary edema and hypotension in severe LV dysfunction 5
• Diltiazem may increase mortality in chronic atrial fibrillation complicated by heart failure 9

Combination Therapy Risks

With Beta-Blockers:

• Non-dihydropyridines combined with beta-blockers risk excessive bradycardia or heart block 6, 4
• Avoid combining verapamil or diltiazem with beta-blockers in patients with LV dysfunction 1
• Long-acting dihydropyridines are preferred when combining with beta-blockers 6, 4

With Other AV Nodal Blockers:

• 86.7% of patients inappropriately discharged on contraindicated CCBs were on multiple AV nodal blocking medications 7
• Diltiazem and verapamil should not be combined with ivabradine due to severe bradycardia risk 4

Hemodynamic Considerations

Hypotension Risk:

• Caution when diastolic BP <60 mm Hg in patients with diabetes or age >60 years (may worsen myocardial ischemia) 4
• Volume-depleted patients are at increased risk for profound hypotension 1

Shock Risk Factors:

• Age >70 years, heart rate >110 bpm, systolic BP <120 mm Hg, and late presentation increase shock risk with CCBs 1

Clinical Context and Common Pitfalls

Acute Coronary Syndromes

In NSTE-ACS, non-dihydropyridine CCBs are only appropriate when:

• Beta-blockers are contraindicated AND
• No LV dysfunction present AND
• No increased cardiogenic shock risk AND
• No significant conduction abnormalities 1

Drug Interactions Requiring Caution

CYP3A4 Interactions:

• Verapamil and diltiazem are moderate CYP3A4 inhibitors and increase statin levels (particularly simvastatin and lovastatin) by 3-5 fold, raising myopathy risk 6, 10
• Diltiazem increases midazolam and triazolam AUC by 3-4 fold with prolonged sedation risk 10
• Carbamazepine levels increase 40-72% with diltiazem, resulting in toxicity 10

Digoxin:

• Verapamil increases serum digoxin levels requiring monitoring 10, 3

Clonidine:

• Sinus bradycardia requiring pacemaker insertion reported with concurrent diltiazem and clonidine 10

Specific Patient Populations

Hypertension and Female Sex:

• Hypertension (OR 7.87) and female sex (OR 3.01) are associated with inappropriate contraindicated CCB prescription 7

Chronic Obstructive Lung Disease:

• Beta-blockers are not contraindicated in COPD without active bronchospasm, making CCBs less necessary as beta-blocker alternatives 1