What are the best calcium channel blockers (CCBs) for treating hypertension and angina?

Best Calcium Channel Blockers for Hypertension and Angina

For hypertension and angina, amlodipine is the best calcium channel blocker based on the strongest evidence from major cardiovascular outcome trials (ALLHAT, ASCOT, VALUE, CAMELOT) demonstrating equivalent or superior blood pressure reduction and cardiovascular event prevention compared to other antihypertensive classes. 1

Classification and Selection Strategy

Dihydropyridines (First Choice for Most Patients)

Amlodipine is the preferred dihydropyridine CCB:

• Demonstrated equivalent cardiovascular outcomes to thiazide diuretics and ACE inhibitors in ALLHAT, with no significant differences in fatal CAD, nonfatal MI, combined CAD outcomes, or all-cause mortality 1
• Showed superiority over beta-blockers in ASCOT for primary prevention 1
• In CAMELOT, reduced hospitalizations for angina by 42% and coronary revascularization by 27% in patients with documented CAD 2
• Provides 24-hour blood pressure control with once-daily dosing 2
• Effective across all patient demographics regardless of sex, race/ethnicity, age, or dietary sodium intake 3

Long-acting dihydropyridines are preferred over nondihydropyridines when combining with beta-blockers to avoid excessive bradycardia or heart block. 1

Nondihydropyridines (Specific Indications)

Diltiazem or verapamil should be selected when:

• Patient has concurrent supraventricular tachycardia or atrial fibrillation requiring rate control 1
• Beta-blockers are contraindicated and heart rate reduction is needed 1
• Patient has baseline tachycardia (diltiazem preferred) 1

Critical contraindications for nondihydropyridines:

• Heart failure or LV systolic dysfunction (must avoid) 1, 4
• Pulmonary edema 4
• Concurrent use with ivabradine (risk of severe bradycardia due to CYP3A4 interaction) 1, 4
• Significant AV nodal disease 1

Dosing for Optimal Efficacy

Amlodipine

• Start: 5 mg once daily 2
• Maximum: 10 mg once daily 2
• For angina: 5-10 mg/day demonstrated significant increases in exercise time (12.8% improvement with 10 mg dose) 2
• For vasospastic angina: Decreased attacks by approximately 4/week compared to placebo 2

Other Dihydropyridines (if amlodipine not tolerated)

• Nifedipine: 120-240 mg daily (long-acting formulations only) 1
• Short-acting nifedipine must be avoided due to reflex sympathetic activation and worsening myocardial ischemia 1, 4

Nondihydropyridines

• Diltiazem: 240-720 mg daily 1
• Verapamil: Titrate based on response 1

Clinical Context and Compelling Indications

Hypertension with Angina

• Amlodipine is first-line for combined hypertension and angina 1, 5
• Reduces myocardial oxygen demand by decreasing peripheral vascular resistance and lowering BP 1
• Increases myocardial oxygen supply through coronary vasodilation 1
• In INVEST, verapamil-based therapy showed similar outcomes to atenolol-based therapy in 22,000 hypertensive patients with chronic CAD, with no difference in cardiovascular death, MI, or coronary revascularization 1

Vasospastic (Prinzmetal's) Angina

• CCBs are the treatment of choice for vasospastic angina 1
• Amlodipine blocks coronary artery constriction and restores blood flow in response to various vasoconstrictive stimuli 2
• Beta-blockers are contraindicated in vasospastic angina 1

Post-Myocardial Infarction

• Beta-blockers remain first choice for at least 6 months post-MI for secondary prevention 1
• CCBs do not improve survival in post-MI patients and do not prevent ventricular dilatation as effectively as ACE inhibitors 1
• CCBs are alternatives when beta-blockers are contraindicated 1

Heart Failure

• CCBs do not improve survival in chronic stable angina with or without LV dysfunction 1
• Amlodipine showed no effect on mortality/morbidity in NYHA Class III/IV heart failure patients but was safe (no worsening of heart failure) 2
• Diltiazem and verapamil may have deleterious effects in heart failure and must be avoided 1, 4

Managing Side Effects

Peripheral Edema (Most Common)

• Occurs with all CCBs but more common with dihydropyridines 4, 3
• Incidence can be markedly reduced by combining with ACE inhibitor or ARB 6
• Third-generation CCBs like lercanidipine have significantly less peripheral edema than amlodipine while maintaining comparable efficacy 6, 7

Other Dihydropyridine Side Effects

• Headache, dizziness, flushing, palpitations (especially with short-acting formulations) 1, 3
• Reflex tachycardia (not common with long-acting amlodipine) 1, 2

Nondihydropyridine Side Effects

• Constipation (especially verapamil in elderly) 1
• Bradycardia and AV block (when combined with beta-blockers) 1
• Drug interactions with digoxin and cyclosporine 3

Blood Pressure Goals and Monitoring

• Target BP <130/80 mm Hg in patients with diabetes, chronic renal disease, CAD, or 10-year Framingham risk ≥10% 1
• Target BP <140/90 mm Hg in patients without above conditions 1
• Caution when lowering diastolic BP below 60 mm Hg in patients with diabetes or age >60 years, as this may worsen myocardial ischemia 1
• Most patients require 2 or more drugs to reach goal; when BP is >20/10 mm Hg above goal, initiate two drugs from outset 1

Combination Therapy Strategy

Amlodipine combines effectively with:

• ACE inhibitors or ARBs (reduces edema, improves BP control) 6, 7
• Thiazide diuretics (complementary mechanisms) 1
• Beta-blockers (use long-acting dihydropyridine, not nondihydropyridine) 1

Fixed-dose combinations of amlodipine with ARBs are now available and improve both efficacy and tolerability 6