What is the next best step in managing a patient with non-obstructive coronary artery disease (CAD) who is not on beta blockers, has an unremarkable brain magnetic resonance imaging (MRI) and carotid Doppler, and continues to experience symptoms?

Management of Symptomatic Non-Obstructive CAD

Initiate beta-blocker therapy immediately in this patient with non-obstructive coronary artery disease who continues to experience symptoms, as beta-blockers are the most effective anti-ischemic agents for suppressing myocardial ischemia during routine daily activities and improving clinical outcomes in patients with CAD. 1

Immediate Pharmacologic Management

Beta-Blocker Therapy (First-Line)

• Beta-blockers should be started as initial therapy in patients with documented CAD, even without prior MI (Class IIa recommendation). 2
• Beta-blockers are superior to other anti-ischemic drugs in reducing the magnitude of myocardial ischemia during daily activities and have well-demonstrated cardioprotective effects. 1
• In patients with CAD undergoing contemporary management, beta-blockers provide significant survival benefit, particularly in the first year. 3
• The evidence for beta-blocker benefit in stable coronary disease without prior MI is reasonable (Level of Evidence: C), though not as strong as in post-MI patients. 2

Antiplatelet Therapy

• Aspirin should be initiated in the absence of contraindications (Class IIa recommendation for patients without prior MI). 2
• For patients with coronary luminal irregularities without significant stenosis, aspirin therapy should be continued indefinitely. 4
• Consider adding clopidogrel in high-risk patients with luminal irregularities. 4

Lipid-Lowering Therapy

• High-intensity statin therapy is indicated to reduce cardiovascular events (Class I recommendation for documented CAD). 2, 5
• Target LDL-C should be <100 mg/dL, with consideration for <70 mg/dL in very high-risk patients. 2
• Atorvastatin 40-80 mg daily is appropriate for patients requiring >45% LDL-C reduction. 5
• Aggressive lipid management is recommended even in the absence of significant stenosis. 4

ACE Inhibitor or ARB Therapy

• ACE inhibitors (or ARBs if ACE inhibitor not tolerated) should be considered in all patients with CAD or other vascular disease (Class IIa recommendation). 2
• This is particularly important given the patient's documented coronary disease, even without obstructive lesions. 2

Additional Diagnostic Considerations

Evaluate for Microvascular Dysfunction

• Since the patient has symptoms despite non-obstructive CAD and unremarkable carotid imaging, consider that microvascular dysfunction or coronary vasospasm may be contributing to symptoms. 2
• Multiple physiological mechanisms may contribute to symptoms even without significant stenosis. 4

Consider Advanced Imaging if Symptoms Persist

• Intravascular ultrasound (IVUS) or optical coherence tomography (OCT) can detect vessel wall abnormalities not visible on standard angiography. 2, 4
• These modalities may identify plaque erosion, spontaneous coronary artery dissection (SCAD), or other pathology in patients with MINOCA presentations. 2

Risk Factor Modification

• Aggressive management of all modifiable cardiovascular risk factors is essential, including blood pressure control, smoking cessation, diabetes management, exercise training, and weight reduction. 2, 4
• Blood pressure should be controlled to <140/90 mm Hg (or <150 mm Hg systolic if age ≥80 years). 6

Common Pitfalls to Avoid

• Do not withhold beta-blocker therapy simply because the patient lacks obstructive CAD or prior MI—the evidence supports their use in documented CAD regardless of stenosis severity. 2, 1
• Do not assume symptoms are non-cardiac without considering microvascular dysfunction, vasospasm, or subtle plaque characteristics—these can cause significant ischemia despite non-obstructive disease. 2, 4
• Do not delay statin therapy—lipid-lowering has been demonstrated to decrease adverse ischemic events even in asymptomatic patients with documented CAD. 2

Monitoring and Follow-Up

• Assess symptom response to beta-blocker therapy within 2-4 weeks. 1
• Monitor lipid panel and adjust statin dose to achieve target LDL-C <100 mg/dL. 2, 5
• If symptoms persist despite optimal medical therapy with beta-blockers, consider adding long-acting nitrates as effective antianginal and anti-ischemic agents. 6
• Calcium channel blockers may be added if angina persists despite beta-blockers and nitrates. 6