Management of Angina with Normal Coronary Arteries
Begin with comprehensive cardiovascular risk factor modification and antianginal medical therapy targeting the underlying pathophysiology of microvascular dysfunction or coronary vasospasm, as revascularization offers no benefit in this population. 1
Initial Diagnostic Confirmation
The 2024 ESC guidelines emphasize that angina with non-obstructive coronary arteries (ANOCA) or ischemia with non-obstructive coronary arteries (INOCA) represents a distinct clinical entity requiring specific evaluation beyond simply excluding obstructive disease. 1
Key diagnostic considerations:
Confirm objective evidence of ischemia through stress testing (exercise ECG, stress imaging, or functional imaging) before attributing symptoms to microvascular dysfunction, as up to 40% of patients with angina and normal coronaries may have demonstrable ischemia. 1
Consider invasive coronary reactivity testing with acetylcholine, adenosine, and nitroglycerin to definitively diagnose microvascular dysfunction and coronary vasospasm, as this allows for both diagnostic confirmation and risk stratification for future cardiovascular events (2.5% annual risk of MI, stroke, heart failure, or death). 2
Recognize that women are disproportionately affected by microvascular angina and may present with more frequent symptoms despite less extensive epicardial disease and less severe ischemia on testing compared to men. 1
Medical Management Strategy
First-Line Prognostic Therapy
Initiate the following medications to reduce cardiovascular events, independent of symptom relief: 1
Aspirin 75-325 mg daily for antiplatelet effects in all patients without contraindications, as this reduces vascular events even in the absence of obstructive CAD. 1
High-intensity statin therapy (atorvastatin 80 mg or rosuvastatin 20-40 mg daily) to reduce cardiovascular events by 28-35%, as lipid-lowering benefits extend to patients with microvascular disease. 1
ACE inhibitor therapy (e.g., ramipril 10 mg daily) based on HOPE study evidence showing reduction in cardiovascular death, MI, and stroke in patients with vascular disease, with particular benefit in those with diabetes. 1
Antianginal Symptom Management
The choice of antianginal agent should target the specific pathophysiology:
For microvascular dysfunction (most common presentation): 1, 2
Beta-blockers (e.g., metoprolol 100-400 mg daily in divided doses) as initial therapy to reduce myocardial oxygen demand and improve coronary perfusion pressure. 1, 3
Calcium channel blockers if beta-blockers are contraindicated or ineffective, particularly in patients with suspected vasospastic component. 1
Ranolazine 500-1000 mg twice daily as add-on therapy when first-line agents fail to control symptoms, as it has demonstrated efficacy in reducing angina frequency (mean reduction of 1.0 attacks/week) and nitroglycerin use without affecting heart rate or blood pressure. 4, 2
For suspected coronary vasospasm: 1
Calcium channel blockers are preferred over beta-blockers, as beta-blockers may worsen vasospasm in some patients. 1
Long-acting nitrates can be added for additional symptom control, though tolerance may develop with continuous use. 1
Common pitfall: The 2024 ESC guidelines explicitly state that traditional classification of angina as "typical" versus "atypical" should be abandoned in this population, as patients with both presentations have similar outcomes and the terminology no longer aligns with current understanding of chronic coronary syndromes. 1
Risk Factor Modification
Aggressive lifestyle interventions are essential: 1
Smoking cessation with structured program and pharmacotherapy (nicotine replacement, varenicline, or bupropion) if applicable. 1
Blood pressure control targeting reduction of 30-40% from baseline, as this provides the most significant stroke risk reduction in small vessel disease. 5
Diabetes management with tight glucose control (HbA1c <7%) if present, as diabetes independently predicts adverse outcomes. 5
Physical activity of at least 30 minutes of moderate-intensity exercise daily. 5
Follow-Up and Monitoring
Structured follow-up schedule: 1
Evaluate every 4-6 months during the first year of therapy to assess symptom control, medication adherence, and risk factor modification. 1
Annual evaluations thereafter if clinically stable, with lower threshold for earlier reassessment if symptoms worsen. 1
Repeat testing is NOT routinely indicated: 1
Do not perform routine periodic cardiac testing without a change in clinical status, as no evidence supports this practice. 1
Reserve repeat stress testing for patients with significant change in clinical status (new symptoms, worsening functional capacity, or development of heart failure). 1
Avoid repeated coronary angiography in patients with no change in clinical status and previously documented non-obstructive CAD. 1
Prognosis and Patient Counseling
The prognosis for mortality is generally favorable (annual cardiovascular mortality typically <1%), but morbidity remains high with continuing chest pain episodes and frequent hospital readmissions. 1, 2
Emerging evidence suggests that identification of impaired endothelial dysfunction may identify a subgroup at risk for future development of atherosclerotic coronary disease with less benign prognosis than previously thought. 1
Critical caveat: Gender differences in treatment response are substantial—in the CARISA trial, improvement in exercise tolerance in females was only 33% of that in males at the 1000 mg ranolazine dose, and mean reduction in weekly angina attacks was 0.3 for females versus 1.3 for males in the ERICA trial. 4 This underscores the need for more aggressive symptom management strategies in women.