What is the initial management approach for a patient with stable angina, considering lifestyle modifications and pharmacological therapy?

Management of Stable Angina

Dual Treatment Goals: Mortality Reduction First, Then Symptom Control

All patients with stable angina should receive aspirin 75-325 mg daily, statin therapy, and an ACE inhibitor (if hypertension, diabetes, LV dysfunction, or prior MI present) to prevent myocardial infarction and death, while beta-blockers serve as first-line therapy for both mortality reduction (especially post-MI) and symptom control. 1, 2

The treatment hierarchy prioritizes therapies that reduce mortality over those that merely relieve symptoms. 1 When two strategies equally alleviate angina, the one with mortality benefit takes precedence. 1

Mandatory Lifestyle Modifications

Physicians must always recommend the following alongside pharmacotherapy: 1

• Smoking cessation (highest priority lifestyle intervention) 1, 2
• Regular exercise 1, 2
• Appropriate diet and weight management 2
• Strict diabetic control (if applicable) 2
• Blood pressure control 2

Pharmacological Management Algorithm

Step 1: Mortality-Reducing Agents (Start Immediately in All Patients)

Aspirin 75-325 mg daily 1, 2, 3

• Meta-analysis of >200 trials shows 75-150 mg daily equals 160-325 mg daily in efficacy 1
• Doses <75 mg show less benefit 1
• If aspirin contraindicated: use clopidogrel 1

Statin therapy (regardless of baseline cholesterol) 1, 2, 3

• Reduces adverse ischemic events in documented CAD 1
• Level A evidence for mortality reduction 1

ACE inhibitor 1, 2, 3

• Mandatory if: hypertension, heart failure, LV dysfunction, prior MI, or diabetes 1, 2
• Level A evidence in these populations 1

Step 2: First-Line Anti-Anginal Therapy

Beta-blockers at optimal doses: 1, 2, 3, 4

• Bisoprolol 10 mg once daily 2
• Metoprolol CR 200 mg once daily 2
• Atenolol 100 mg daily 2

Beta-blockers provide dual benefit: mortality reduction (especially post-MI, Level A evidence) and symptom control (Level B evidence without prior MI). 1, 2 All beta-blockers appear equally effective. 4 Diabetes is NOT a contraindication—diabetic patients benefit equally or more. 2

Critical pitfall: Beta-blockers are absolutely contraindicated in vasospastic (Prinzmetal's) angina, as they cause unopposed alpha-mediated vasoconstriction. 3

Step 3: Sublingual Nitroglycerin for Acute Relief

Short-acting nitrates for immediate symptom relief and situational prophylaxis (Level B evidence). 1, 2 Patients should carry sublingual nitroglycerin or spray at all times. 1

Warning: An angina attack not responding to sublingual nitroglycerin should be treated as possible myocardial infarction. 2

Step 4: Second-Line Anti-Anginal Therapy (If Beta-Blockers Fail, Contraindicated, or Not Tolerated)

Long-acting calcium channel blockers (Level B evidence): 1, 2, 3, 4

• Dihydropyridines (e.g., amlodipine 5-10 mg daily): preferred for sustained 24-hour effects 1, 5
• Non-dihydropyridines (verapamil 240-480 mg/day or diltiazem 180-360 mg/day): equally effective 3, 4

OR Long-acting nitrates (Level B evidence) 1, 2

• Considered third-line by some guidelines due to need for nitrate-free interval to avoid tolerance 4
• ACC/AHA writing committee prefers calcium antagonists over long-acting nitrates for maintenance therapy 1

Critical pitfall: Avoid immediate-release or short-acting dihydropyridine calcium antagonists—they increase adverse cardiac events. 2

Critical pitfall: Do NOT combine verapamil or diltiazem with beta-blockers in heart failure patients due to negative inotropic effects. 2

Step 5: Combination Therapy (If Monotherapy Insufficient)

Add calcium channel blocker OR long-acting nitrate to beta-blocker (Level B evidence). 1, 2 Optimize one drug's dosing before adding another. 2

Alternative approach: Switch drug combinations before attempting three-drug regimen. 2 Using three anti-anginal drugs simultaneously may provide less symptomatic protection than two drugs. 2

Step 6: Third-Line Add-On Therapy (If Two Drugs Fail)

Ranolazine as add-on therapy (particularly effective for microvascular angina): 2, 6

• Dose: 500 mg twice daily for 1 week, then 1000 mg twice daily 6
• CARISA trial showed statistically significant increases in exercise duration and time to angina at both 750 mg and 1000 mg doses 6
• ERICA trial demonstrated significant decreases in angina frequency (p=0.028) when added to amlodipine 10 mg 6
• No tolerance develops after 12 weeks; no rebound angina upon discontinuation 6

Nicorandil (alternative add-on, but safety data in heart failure uncertain) 2

Critical pitfall: Do NOT combine nicorandil with nitrates—lacks additional efficacy. 2

Critical pitfall: Do NOT combine ivabradine with non-dihydropyridine calcium channel blockers or strong CYP3A4 inhibitors. 2

Step 7: Coronary Revascularization

Indications for coronary arteriography with view to revascularization: 2, 3

• Symptoms not satisfactorily controlled by two anti-anginal drugs 2
• Persistent angina despite optimal medical therapy 2, 3

PCI: Effective when anatomically suitable lesions present 2, 3

CABG: Highly effective for symptom relief AND reduces mortality in specific subgroups: 2, 3, 4

• Left main stem stenosis
• Proximal LAD stenosis
• Three-vessel disease with impaired LV function

Special Considerations for Asymptomatic Patients with Known CAD

Even without symptoms, these patients require: 1

• Aspirin (if prior MI: Level A evidence) 1
• Beta-blockers (if prior MI: Level B evidence) 1
• Statin therapy (Level A evidence for documented CAD or type 2 diabetes) 1
• ACE inhibitor (if CAD plus diabetes, systolic dysfunction, or both: Level A evidence) 1

Common Pitfalls to Avoid

• Poor medication adherence is a common cause of treatment failure—always assess compliance first 2
• Dipyridamole should NOT be used—usual oral doses can enhance exercise-induced myocardial ischemia (Level B evidence) 1
• Chelation therapy should NOT be used (Level B evidence) 1
• Do NOT use immediate-release dihydropyridine calcium antagonists 2
• Do NOT combine verapamil/diltiazem with beta-blockers in heart failure 2
• Recognize vasospastic angina early—requires calcium channel blockers, NOT beta-blockers 3

Evidence Quality Note

The recommendations prioritize the most recent high-quality guidelines from the European Society of Cardiology (2025) 2 and American College of Physicians/American College of Cardiology (2004) 1, supplemented by FDA drug labels for specific agents 5, 6. No antianginal drug has been proven to reduce cardiovascular mortality or MI rates, but they significantly improve quality of life. 3, 7