What is the recommended management for angina?

Management of Angina

Start all patients with stable angina on aspirin 75-150 mg daily, a beta-blocker titrated to full dose, a statin, and provide sublingual nitroglycerin for acute symptom relief. 1, 2

Immediate Symptom Relief

• Provide short-acting sublingual nitroglycerin to all patients for acute angina attacks and situational prophylaxis before activities that may trigger symptoms 1, 2
• Sublingual nitroglycerin should be taken 2-3 minutes before anticipated angina-provoking activities 1
• If sublingual preparations are ineffective, consider buccal nitroglycerin formulations, which are more effective than sublingual 1
• Critical warning: An angina attack unresponsive to short-acting nitroglycerin should be treated as a possible myocardial infarction 2
• Patients must be instructed never to abruptly stop or run out of medications, particularly beta-blockers 1, 3

Prognostic Medications (Reduce Mortality and Morbidity)

These medications improve outcomes beyond symptom control:

• Aspirin 75-150 mg daily for all patients unless absolutely contraindicated; if contraindicated, use clopidogrel 75 mg daily 1, 2
• Statin therapy for all patients with coronary disease regardless of baseline cholesterol 1, 2
• ACE inhibitor for all patients with stable angina, particularly those with hypertension, heart failure, LV dysfunction, prior MI, or diabetes 1, 2
• Beta-blocker for all patients, especially those with prior MI or heart failure 1, 2

First-Line Anti-Anginal Therapy Algorithm

Step 1: Initiate Beta-Blocker Monotherapy

• Beta-blockers are the preferred first-line therapy for most patients with stable angina 1, 4, 2
• Target doses: bisoprolol 10 mg once daily, metoprolol CR 200 mg once daily, or atenolol 100 mg daily 2
• Titrate to achieve resting heart rate of 55-60 bpm for optimal anti-anginal effect 4
• Optimize the dose of one drug before adding another—this is more effective than using multiple drugs at subtherapeutic doses 1
• Beta-blockers have Level A evidence for patients with prior MI and Level B evidence for those without prior MI 1

Beta-blocker contraindications and cautions 1, 4, 3:

• Absolute contraindications: sick sinus syndrome, atrioventricular conduction disorders, severe bradycardia
• Relative contraindications: asthma, symptomatic peripheral vascular disease, COPD
• Never abruptly discontinue beta-blockers in patients with coronary disease—taper over 1-2 weeks to avoid severe exacerbation of angina, MI, or ventricular arrhythmias 3

Step 2: If Beta-Blockers Are Contraindicated or Not Tolerated

• Substitute with a calcium channel blocker (long-acting) OR long-acting nitrate OR nicorandil 1, 4
• Calcium channel blockers are particularly appropriate for patients with vasospastic angina, microvascular angina, or hypertension 4
• For vasospastic angina specifically, use high-dose calcium antagonists: up to 480 mg/day verapamil, 260 mg/day diltiazem, or 120 mg/day nifedipine 1
• There is no clear evidence favoring one substitution agent over another, so choose the cheapest preparation the patient can tolerate and comply with 1

Step 3: If Beta-Blocker Monotherapy Is Insufficient

• Add a dihydropyridine calcium channel blocker (e.g., amlodipine, nifedipine long-acting) 1, 4
• This combination has Level B evidence for symptom control 1
• Critical pitfall: Avoid combining non-dihydropyridine calcium channel blockers (verapamil, diltiazem) with beta-blockers due to excessive bradycardia risk 4

Step 4: If Two-Drug Combination Fails

• Consider switching drug combinations before attempting a three-drug regimen—three drugs may provide less symptomatic protection than two drugs 1, 2
• If adding a third drug, options include long-acting nitrates, nicorandil, ranolazine, or trimetazidine 1, 4
• Monitor the effect of any third drug and discontinue if ineffective 1
• Patients uncontrolled on full doses of two drugs should be referred to cardiology for angiography rather than empirically adding a third drug 1

Long-Acting Nitrate Considerations

• Long-acting nitrates are effective initially but tolerance develops rapidly with continuous use 1, 5
• Mandatory nitrate-free interval of 10-12 hours daily to prevent tolerance 4, 5
• For transdermal patches, remove at bedtime and reapply in the morning; use patches of at least 10 mg 1, 6
• Pentaerythritol tetranitrate (PETN) may not develop tolerance like other nitrates, as it does not generate reactive oxygen species 5
• Contraindications: hypertrophic cardiomyopathy, concurrent phosphodiesterase inhibitor use 4

Special Populations

Vasospastic Angina

• Smoking cessation is essential 1
• First-line: High-dose calcium channel blockers (dihydropyridines preferred) 1, 4
• Add-on: Long-acting nitrates or nicorandil for refractory symptoms 1, 4
• Spontaneous remission occurs in approximately 50% of patients after 1 year of treatment; consider tapering therapy 6-12 months after symptoms resolve 1

Microvascular Angina

• Ranolazine and trimetazidine are particularly effective 4

Patients with Diabetes

• Beta-blockers may mask tachycardia from hypoglycemia, though dizziness and sweating remain 3
• ACE inhibitors provide particular benefit in diabetic patients with coronary disease 1

Patients with Pheochromocytoma

• Beta-blockers must only be given after alpha-blocker initiation to avoid paradoxical hypertension 3

Medications to Avoid

• Immediate-release or short-acting dihydropyridine calcium antagonists increase adverse cardiac events and should be avoided 1, 2
• Dipyridamole and chelation therapy have no role in angina management 1

When to Refer for Revascularization

• All patients with clinically certain angina should be referred for risk stratification to identify those who would benefit from prognostic investigation 1, 2
• Refer patients with symptoms uncontrolled on two drugs at maximal doses for coronary angiography, not exercise testing 1
• Refer patients with pain on minimal exertion, uncertain diagnosis, or unacceptable interference with lifestyle 1
• PCI is effective for anatomically suitable lesions when medical therapy fails 2
• CABG reduces mortality in left main stenosis, proximal LAD stenosis, or three-vessel disease with impaired LV function 2

Common Pitfalls

• Poor medication adherence is a frequent cause of treatment failure—always assess compliance before escalating therapy 1
• Failing to provide adequate nitrate-free intervals leads to tolerance and treatment failure 4, 5
• Abruptly discontinuing beta-blockers can precipitate severe angina exacerbation, MI, or arrhythmias 3
• Using three anti-anginal drugs simultaneously may be less effective than optimizing two drugs 1, 2