What is the first line treatment for a patient with stable angina?

First-Line Treatment for Stable Angina

Beta-blockers are the recommended first-line antianginal therapy for stable angina, with bisoprolol 10 mg once daily, metoprolol CR 200 mg once daily, or atenolol 100 mg daily as optimal doses. 1, 2, 3

Mandatory Foundational Therapy (Start Immediately)

Before addressing symptoms, three medications must be initiated in all patients without contraindications, as these reduce mortality and prevent MI:

• Aspirin 75-100 mg daily - Non-negotiable for all patients, reduces cardiovascular mortality and morbidity 4, 1, 2, 3
• High-intensity statin therapy - Mandatory regardless of baseline cholesterol, targeting LDL-C <70 mg/dL when possible 1, 2, 3
• Sublingual nitroglycerin - For immediate symptom relief and situational prophylaxis before known triggers 1, 2, 3

First-Line Antianginal Therapy

Beta-blockers are the preferred initial agent because they provide both symptom control and mortality benefits in post-MI patients 4, 1, 2, 3, 5. The evidence supporting beta-blockers as first-line is based on their proven efficacy in reducing cardiac events when used as secondary prevention and their demonstrated mortality reduction in patients with hypertension 3.

Optimal Beta-Blocker Dosing:

• 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 2.

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

If beta-blockers are contraindicated, not tolerated, or symptoms persist despite optimal dosing, the following alternatives should be considered:

Calcium Channel Blockers (CCBs):

• Amlodipine is the preferred CCB alternative, as it is effective for symptom control and safe in heart failure 4, 1
• Amlodipine 5-10 mg daily has been shown effective in exercise-induced angina, with the 10 mg dose increasing exercise time by an average of 12.8% (63 seconds) 6
• Avoid combining verapamil or diltiazem with beta-blockers in heart failure patients due to negative inotropic effects 2, 3

Long-Acting Nitrates:

• Effective antianginal treatment and safe in heart failure 4
• Require a nitrate-free interval to avoid tolerance development 4, 7
• Patients are unprotected during the nitrate-free period (typically at night and early morning) 7

Ivabradine:

• Should be considered in patients in sinus rhythm who cannot tolerate beta-blockers 4
• Do not combine with non-dihydropyridine CCBs or strong CYP3A4 inhibitors 2

Third-Line Add-On Therapy

If symptoms persist despite two antianginal drugs at optimal doses:

• Ranolazine may be added, particularly effective for microvascular angina 2, 3
• Nicorandil may be considered, though safety data in heart failure is uncertain 4, 2
• Avoid combining nicorandil with nitrates as it lacks additional efficacy 2

Additional Mandatory Interventions

ACE Inhibitors:

Indicated for patients with hypertension, heart failure, LV dysfunction, prior MI with LV dysfunction, or diabetes 1, 3

Risk Factor Modification:

• Smoking cessation - Single most important modifiable risk factor directly impacting mortality 2, 3
• Blood pressure control: target <130/80 mmHg for diabetes/renal disease, <130/85 mmHg for established coronary disease 2
• Aerobic exercise: 150-300 minutes/week at moderate intensity or 75-150 minutes at vigorous intensity 2, 3
• Mediterranean diet emphasizing vegetables, fruit, fish, and poultry 2, 3

Treatment Optimization Algorithm

1. Optimize dosing of the first drug before adding a second 1
2. If monotherapy fails, switch to another class rather than adding a second drug initially 7
3. If maximum monotherapy is only partially effective, add a second agent with non-additive adverse effects 7
4. Switch drug combinations before attempting a three-drug regimen - triple therapy may provide less symptomatic protection than two drugs 1, 7

When to Consider Revascularization

Coronary arteriography should be undertaken when symptoms are not satisfactorily controlled by two antianginal drugs at optimal doses, with a view to revascularization 1, 2, 3:

• PCI is effective for anatomically suitable lesions 1, 3
• CABG reduces mortality in specific high-risk subgroups: left main stenosis ≥50%, three-vessel disease (especially with impaired LV function), or two-vessel disease with proximal LAD stenosis 1, 2, 3

Critical Pitfalls to Avoid

• Never use immediate-release or short-acting dihydropyridine calcium antagonists - they can increase adverse cardiac events 1
• An angina attack not responding to sublingual nitroglycerin should be regarded as possible MI 1
• Always assess medication adherence - poor adherence is a common cause of treatment failure 1
• Avoid combining beta-blockers with verapamil or diltiazem in heart failure due to negative inotropic effects 2, 3

Follow-Up Protocol

• Initial review at 2-4 weeks after drug initiation to assess response 2
• Routine follow-up every 4-6 months to assess angina frequency, nitroglycerin use, functional capacity, and medication adherence 2
• Repeat stress testing when there is significant change in symptoms or new symptoms suggesting progression 2