What is the first-line therapy for managing angina?

First-Line Anti-Anginal Therapy

Beta-blockers and/or calcium channel blockers are the recommended first-line therapies for managing stable angina, with the choice tailored to the patient's hemodynamic profile, comorbidities, and the underlying mechanism of ischemia. 1, 2

Initial Therapy Selection

Beta-Blockers as Primary First-Line

• Beta-blockers should be the initial choice for most patients with stable angina, particularly those with prior myocardial infarction, heart failure, hypertension, or high resting heart rate (>60 bpm). 1, 2, 3
• Target heart rate should be 55-60 beats per minute when using beta-blockers for antianginal purposes. 1, 2
• Beta-blockers reduce myocardial oxygen demand by decreasing heart rate, contractility, and blood pressure. 2
• Beta-blockers are the only antianginal medication proven to improve long-term cardiovascular outcomes when given within 1 year after acute myocardial infarction. 1, 2
• All beta-blockers appear equally effective for angina relief. 3

Calcium Channel Blockers as Alternative First-Line

• Calcium channel blockers are equally effective as beta-blockers for symptom control and should be used when beta-blockers are contraindicated, not tolerated, or in specific clinical scenarios. 1, 2, 3
• Both dihydropyridines (amlodipine, nifedipine) and non-dihydropyridines (verapamil, diltiazem) are effective options. 2
• Calcium channel blockers are particularly preferred for vasospastic angina, where they directly block coronary artery vasospasm. 2, 4
• Amlodipine 5-10 mg daily has demonstrated significant increases in exercise time (12.8% improvement at 10 mg dose) and decreased angina attack rates in chronic stable angina. 5

Specific Clinical Scenarios

For vasospastic (Prinzmetal's) angina:

• Calcium channel blockers are first-line therapy (verapamil 240-480 mg/day, diltiazem 180-360 mg/day, or nifedipine 60-120 mg/day). 4
• Beta-blockers are absolutely contraindicated in vasospastic angina as they can cause unopposed alpha-mediated vasoconstriction and worsen coronary spasm. 4

For patients with:

• Heart failure with reduced ejection fraction: Beta-blockers are strongly preferred. 1, 2
• COPD or peripheral arterial disease: Calcium channel blockers are preferred over beta-blockers. 1
• Low heart rate (<50 bpm): Calcium channel blockers or other non-rate-lowering agents should be used instead of beta-blockers. 6
• Microvascular angina: Beta-blockers with a RAS blocker and statin are recommended. 6

Combination First-Line Therapy

• Many patients require combination therapy with both a beta-blocker and a dihydropyridine calcium channel blocker for adequate symptom control. 1, 2
• The combination of beta-blocker plus calcium channel blocker has demonstrated effectiveness across multiple outcomes. 7
• When combining, use a beta-blocker with a dihydropyridine calcium channel blocker (e.g., amlodipine) to avoid excessive bradycardia or heart block. 2

Essential Concurrent Therapy

• All patients must be prescribed sublingual nitroglycerin (0.3-0.6 mg) or sublingual isosorbide dinitrate (2.5-10 mg) for immediate relief of acute angina episodes. 2, 8
• Patients should call emergency services if symptoms are unimproved or worsening 5 minutes after one dose. 8
• Patients should sit when first using sublingual nitrates to avoid hypotension-related falls. 8

Critical Safety Considerations

• Never abruptly discontinue beta-blockers in patients with coronary artery disease—taper over 1-2 weeks to avoid severe exacerbation of angina, myocardial infarction, or ventricular arrhythmias. 2, 9
• Beta-blockers should be titrated to full dose before adding other agents. 2
• In patients already taking beta-blockers whose angina becomes unstable, adding a calcium channel blocker (particularly nifedipine) is more effective than switching agents. 10

Second-Line Agents (Not First-Line)

• Long-acting nitrates, ivabradine, nicorandil, ranolazine, and trimetazidine are second-line agents added when first-line therapy is inadequate, contraindicated, or not tolerated. 1, 2
• No evidence exists that any antianginal medication improves long-term cardiovascular outcomes except beta-blockers post-MI. 1, 2
• Long-acting nitrates require a 10-14 hour nitrate-free interval daily to prevent tolerance. 2, 8

Evidence Quality Note

• There is no robust evidence from direct head-to-head comparisons that any antianginal drug is superior to another for symptom control, with equivalence demonstrated only for beta-blockers, calcium channel blockers, and ivabradine. 1, 11
• Current first-line recommendations are based on decades of clinical experience, safety profiles, and the unique prognostic benefit of beta-blockers post-MI rather than superiority in symptom control alone. 1, 11