What is the stepwise medication approach to manage angina?

Stepwise Medication Management of Angina

All patients with angina should receive short-acting sublingual nitroglycerin for immediate symptom relief, followed by a beta-blocker as first-line regular therapy, titrated to full dose before considering additional agents. 1, 2

Initial Therapy for All Patients

Immediate Symptom Relief

• Prescribe sublingual nitroglycerin (glyceryl trinitrate) for all patients to use as needed for acute angina episodes and before activities known to trigger symptoms 1, 2
• Instruct patients to sit during first use to prevent hypotension 3
• If sublingual preparations are ineffective, consider buccal formulations 1

Prognostic Medications (Start Immediately)

These medications improve survival but do not relieve symptoms:

• Aspirin 75-300 mg daily for all patients unless contraindicated 1, 3
• Statin therapy regardless of cholesterol levels 3
• ACE inhibitors for patients with coexisting hypertension, heart failure, LV dysfunction, prior MI with LV dysfunction, or diabetes 3

Step 1: Beta-Blocker Monotherapy

Start with a beta-1 selective blocker and titrate to full dose before adding other agents 1, 2:

• Metoprolol 200 mg once daily 3
• Atenolol 100 mg daily 3
• Bisoprolol 10 mg once daily 3

Key considerations:

• Beta-blockers reduce myocardial oxygen demand by decreasing heart rate, contractility, and blood pressure 2
• Particularly beneficial in patients with prior myocardial infarction or heart failure 2
• Never discontinue abruptly in patients with coronary artery disease—taper over 1-2 weeks to avoid severe exacerbation of angina, MI, or ventricular arrhythmias 1, 4
• Optimize the dose of one drug before adding another, as three anti-anginal drugs may provide less symptomatic protection than two 1

Step 2: If Beta-Blocker Intolerant or Contraindicated

Switch to calcium channel blocker (CCB) monotherapy 1, 2:

• Dihydropyridines (amlodipine, nifedipine): reduce afterload and cause coronary vasodilation 2
• Non-dihydropyridines (verapamil, diltiazem): reduce heart rate and contractility 2
• CCBs are particularly effective for vasospastic angina 2

Alternative first-line options if beta-blockers not tolerated:

• Long-acting nitrates (with 10-12 hour nitrate-free interval to prevent tolerance) 1, 2
• Nicorandil 1
• Ivabradine (sinus node inhibitor) for patients with beta-blocker intolerance 1, 2

Step 3: If Beta-Blocker Monotherapy Insufficient

Add a dihydropyridine calcium channel blocker (amlodipine or nifedipine) to the beta-blocker 1:

• This combination is synergistic and often required for adequate symptom control 2
• Beta-blockers prevent reflex tachycardia from dihydropyridine CCBs 3

Step 4: If Two-Drug Combination Unsuccessful

Before attempting a three-drug regimen, switch drug combinations rather than adding a third agent 1:

• Substitute the CCB with a long-acting nitrate or nicorandil 1
• Ensure nitrate-free interval of 10-12 hours to avoid tolerance 1, 2

Alternative second-line agents to add or substitute:

• Ranolazine: reduces angina frequency without affecting heart rate or blood pressure; particularly useful in patients with low heart rate/blood pressure 2
• Trimetazidine: metabolic agent that improves cardiac metabolism; beneficial in microvascular angina 2
• Ivabradine: selective heart rate reduction; alternative for beta-blocker intolerance 2
• Nicorandil: potassium channel activator with nitrate-like effects 2

Critical evidence gap: No direct comparisons demonstrate superiority of first-choice over second-choice agents 3, 5, and recent systematic reviews show equivalence among beta-blockers, CCBs, and ivabradine 5

Step 5: Refractory Angina

If symptoms remain uncontrolled on full doses of two drugs, refer to cardiology for angiography rather than adding a third drug 1:

• Consider revascularization (PCI or CABG) for anatomically suitable lesions 3
• Evaluate for microvascular angina, which affects up to 40% of angina patients and may persist after revascularization 3

Special Considerations

Vasospastic (Prinzmetal's) Angina

• Calcium channel blockers and long-acting nitrates are first-line 6
• Beta-blockers are absolutely contraindicated as they cause unopposed alpha-mediated coronary vasoconstriction 6
• Smoking cessation is mandatory 6

Important Contraindications and Warnings

• Beta-blockers: avoid in bronchospastic disease, severe bradycardia, heart block, or vasospastic angina 2, 6, 4
• Non-dihydropyridine CCBs: avoid in heart failure with reduced ejection fraction or significant conduction abnormalities 2
• Nitrates: require daily nitrate-free interval; avoid with phosphodiesterase-5 inhibitors 2

Common Pitfall

Poor medication adherence is a major factor when drug therapy appears unsuccessful—verify compliance before escalating therapy 1