What is the recommended management for stable angina?

Management of Stable Angina

All patients with stable angina should immediately receive aspirin 75-100 mg daily, statin therapy targeting LDL <70 mg/dL, and beta-blockers as first-line anti-anginal therapy, combined with sublingual nitroglycerin for acute symptom relief and aggressive risk factor modification including mandatory smoking cessation. 1, 2

Dual Treatment Goals: Prognostic vs. Symptomatic Therapy

Management fundamentally requires two distinct therapeutic strategies that cannot be achieved with the same medications 1, 3:

Prognostic therapy (preventing MI and death):

• Aspirin 75-100 mg daily for all patients without contraindications 1, 2
• Statin therapy regardless of baseline cholesterol, targeting LDL <70 mg/dL when possible 1, 2
• ACE inhibitors for patients with hypertension, heart failure, LV dysfunction, prior MI with LV dysfunction, or diabetes 1, 2

Symptomatic therapy (reducing angina and improving quality of life):

• Beta-blockers, calcium channel blockers, or long-acting nitrates 1, 3
• These anti-anginal drugs do not improve survival 3

Step-by-Step Anti-Anginal Drug Algorithm

Step 1: First-Line 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:

• Bisoprolol 10 mg once daily 1
• Metoprolol CR 200 mg once daily 1
• Atenolol 100 mg daily 1

Critical point: Diabetes is NOT a contraindication for beta-blockers; diabetic patients benefit equally or more from their use 1

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

Add or substitute with a dihydropyridine calcium channel blocker (e.g., amlodipine) if beta-blockers are contraindicated, not tolerated, or symptoms persist despite optimal dosing 1, 3:

• Long-acting dihydropyridine CCBs (amlodipine) are preferred 1
• Avoid immediate-release or short-acting dihydropyridine CCBs as they increase adverse cardiac events 1
• Do NOT combine verapamil or diltiazem with beta-blockers in patients with heart failure due to negative inotropic effects 1

Long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid tolerance 1, 4:

• Nitrates combined with beta-blockers provide synergistic anti-ischemic effects by blocking reflex tachycardia 3

Step 3: Add-On Therapy for Persistent Symptoms

Consider ranolazine as add-on therapy if symptoms persist despite two anti-anginal drugs, particularly for microvascular angina 1:

• Ranolazine 500-1000 mg twice daily reduces angina frequency and nitroglycerin use when added to amlodipine or beta-blockers 5
• In the CARISA trial, ranolazine 750-1000 mg twice daily significantly increased exercise duration and time to angina (p<0.05) 5
• In the ERICA trial, ranolazine 1000 mg twice daily added to amlodipine 10 mg daily significantly decreased angina attacks (p=0.028) and nitroglycerin use 5

Alternative second-choice medications include ivabradine, nicorandil, and trimetazidine, though no direct comparisons have demonstrated superiority over first-choice agents 1, 3

Step 4: Revascularization

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

• PCI is effective for patients with angina not satisfactorily controlled by medical treatment when anatomically suitable lesions are present 1, 2
• CABG is highly effective for symptom relief and reduces mortality in specific subgroups: left main stem stenosis, proximal LAD stenosis, or three-vessel disease with impaired LV function 1, 2

Acute Symptom Relief

Short-acting sublingual nitroglycerin is essential for immediate symptom relief and situational prophylaxis 1, 2:

• Patients should sit during first use to prevent hypotension 3
• An attack of angina that does not respond to short-acting nitroglycerin should be regarded as a possible myocardial infarction 1

Risk Factor Modification

Smoking cessation is mandatory as it directly impacts mortality 2:

• Nicotine patches can be safely used to help patients with coronary artery disease stop smoking 2

Blood pressure control with target <130/80 mmHg for patients with diabetes or renal disease, and <130/85 mmHg for other patients with established coronary disease 6

Physical activity of 150-300 minutes per week at moderate intensity or 75-150 minutes at vigorous intensity 2:

• Exercise increases tolerance, reduces symptoms, and favorably affects weight, blood lipids, blood pressure, and glucose tolerance 6

Mediterranean diet with emphasis on vegetables, fruit, fish (at least once weekly), and poultry 6, 2

Diabetes management with good glycemic control and attention to other risk factors; multifactorial intervention markedly reduces cardiovascular complications 6

Critical Pitfalls to Avoid

• Using three anti-anginal drugs simultaneously may provide less symptomatic protection than two drugs 1
• Poor medication adherence is a common cause of treatment failure and should always be assessed 1
• Avoid combining verapamil or diltiazem with beta-blockers in heart failure patients 1
• Avoid unopposed COX-2 inhibition (without effective simultaneous platelet COX-1 inhibition) 6
• Avoid ibuprofen with aspirin as it prevents aspirin from irreversibly acetylating platelet COX-1 6
• Diclofenac can be used with aspirin as it does not interfere with aspirin's antiplatelet effects 6

Diagnostic Approach

Exercise ECG is the initial non-invasive test of choice to confirm diagnosis and determine prognosis, with attention to hemodynamic response, workload achieved, clinical features, symptoms, and ST-segment response 6, 1, 3:

• Alternative investigations (myocardial perfusion scintigraphy, stress echocardiography) are valuable when exercise ECG is not possible or interpretable, or to demonstrate extent and localization of ischemia 6, 1
• Careful interpretation of chest pain is particularly important in women, as classical symptoms are less reliable indicators of coronary disease compared to men 6, 1, 3

Special Considerations

Up to 40% of patients may have microvascular angina (coronary microvascular dysfunction) rather than obstructive epicardial disease, explaining why ischemia can persist after successful revascularization 2, 3

Optimize one drug's dosing before adding another; it is advisable to switch drug combinations before attempting a three-drug regimen 1

Concomitant disorders such as hypertension, diabetes, anemia, and hyperthyroidism should be managed appropriately 6

Sexual intercourse may trigger angina; nitroglycerin prior to intercourse may be helpful, and phosphodiesterase inhibitors (sildenafil, tadalafil, vardenafil) may be used in patients with different levels of cardiovascular risk 6