What is the order of anti-anginal therapy medications?

Order of Anti-Anginal Therapy

Beta-blockers should be initiated as first-line anti-anginal therapy for most patients with chronic stable angina, followed by calcium channel blockers (CCBs) as second-line, with additional agents added sequentially based on symptom control. 1, 2

Treatment Hierarchy

Priority 1: Medications That Reduce Mortality

Before addressing symptom control, initiate these medications that improve survival 1:

• Aspirin 75-100 mg daily for all patients without contraindications 1, 2
• Statin therapy regardless of baseline cholesterol levels 1, 2
• ACE inhibitors for patients with hypertension, heart failure, LV dysfunction, prior MI, or diabetes 2, 3

Step 1: First-Line Anti-Anginal Therapy

Beta-blockers are the preferred initial anti-anginal agent due to mortality benefits in post-MI patients and proven efficacy in symptom control 1, 2:

• Target doses: bisoprolol 10 mg once daily, metoprolol CR 200 mg once daily, or atenolol 100 mg daily 2, 3
• Optimize dosing of the beta-blocker before adding additional agents 2
• Diabetes is NOT a contraindication; diabetic patients benefit equally or more 1

Short-acting nitrates (sublingual nitroglycerin) should be prescribed concurrently for immediate symptom relief and situational prophylaxis 1, 2, 3

Step 2: Second-Line Options When Beta-Blockers Fail or Are Contraindicated

If beta-blockers are contraindicated, not tolerated, or symptoms persist despite optimal dosing, add or substitute with 1, 2:

• Dihydropyridine CCB (e.g., amlodipine) - can be combined with beta-blockers 1
• Long-acting nitrates - effective but require nitrate-free interval to avoid tolerance 1, 2
• Ivabradine - particularly for patients in sinus rhythm who cannot tolerate beta-blockers 1

Important: If combining beta-blocker with CCB, use a dihydropyridine CCB (like amlodipine), NOT verapamil or diltiazem, which have negative inotropic effects and risk worsening heart failure 1

Step 3: Third-Line Add-On Therapy

If symptoms persist despite two anti-anginal drugs, consider adding 1:

• Ranolazine - particularly effective for microvascular angina 1
• Nicorandil - effective but safety data in heart failure uncertain 1
• Trimetazidine - may be considered as add-on therapy 1

Step 4: Revascularization

Coronary revascularization is recommended when angina persists despite treatment with two anti-anginal drugs 1, 2:

• PCI for anatomically suitable lesions 2, 3
• CABG for left main stenosis, proximal LAD stenosis, three-vessel disease, or impaired LV function 2, 3

Critical Pitfalls to Avoid

• Never use immediate-release or short-acting dihydropyridine CCBs - they increase adverse cardiac events 2
• Do not combine verapamil or diltiazem with beta-blockers in patients with heart failure due to negative inotropic effects 1
• Avoid combining ivabradine with non-dihydropyridine CCBs or strong CYP3A4 inhibitors 1
• Do not combine nicorandil with nitrates - lacks additional efficacy 1
• Avoid dipyridamole - can enhance exercise-induced myocardial ischemia 1
• Using three anti-anginal drugs simultaneously may provide less symptomatic protection than two drugs - switch drug combinations before attempting three-drug regimens 2
• Always assess medication adherence before escalating therapy - poor adherence is a common cause of treatment failure 2

Special Considerations

For patients with heart failure and reduced ejection fraction (LVEF <40%) 1:

• Beta-blockers remain first-line
• Ivabradine should be considered as add-on therapy
• Amlodipine is safe; avoid non-dihydropyridine CCBs

Tailor selection based on 1:

• Patient comorbidities (COPD, diabetes, heart failure)
• Concomitant medications
• Underlying pathophysiology (vasospastic angina benefits from dihydropyridine CCB and nitrates; microvascular angina responds to ranolazine)
• Local drug availability and cost