Treatment for Non-Obstructive Coronary Artery Disease
Treatment of non-obstructive CAD must be mechanism-based and guided by invasive coronary function testing to identify the specific underlying pathophysiology—whether coronary microvascular dysfunction, endothelial dysfunction, or vasospasm—with targeted pharmacotherapy selected accordingly. 1
Universal Foundation for All Patients
Regardless of the specific mechanism, all patients with non-obstructive CAD require:
- Aggressive cardiovascular risk factor management including hypertension control (target systolic BP 120-130 mmHg for general population, 130-140 mmHg if >65 years), dyslipidemia treatment, and diabetes optimization 1, 2
- Statin therapy with goal of reducing LDL-C by ≥50% from baseline and/or achieving LDL-C <1.4 mmol/L (<55 mg/dL); if not achieved with maximally tolerated statin after 4-6 weeks, add ezetimibe 2, 3
- Lifestyle modifications including heart-healthy diet (Mediterranean, DASH), regular exercise, stress management, weight control, and smoking cessation 1
- Aspirin 75-100 mg daily for secondary prevention in patients with previous MI or revascularization 2
The 2024 European Society of Cardiology guidelines represent a paradigm shift, emphasizing that medical therapy selection should be based on invasive coronary function testing results (Class IIa, Level A recommendation) rather than empirical treatment 1.
Mechanism-Specific Pharmacotherapy
For Coronary Microvascular Dysfunction (CMD)
Diagnosed by reduced coronary flow reserve (CFR) and/or elevated index of microcirculatory resistance (IMR):
- First-line: Beta-blockers (Class IIa, Level B) 1
- Alternative or adjunctive options:
- ACE inhibitors should also be considered, as data indicate symptom improvement in patients with CMD and reduced CFR 1
Critical caveat: Avoid combining ivabradine with diltiazem or verapamil 1.
For Endothelial Dysfunction
- ACE inhibitors (Class IIa, Level B) are the primary recommendation for symptom control 1
- ARBs if ACE inhibitors are not tolerated 2
For Vasospastic Angina
This requires the most aggressive approach due to risk of potentially fatal complications:
- Calcium channel blockers (Class I, Level A)—this is the strongest recommendation 1
- High-dose CCB therapy may be necessary: Combination of dihydropyridine and non-dihydropyridine CCBs may be required, with unusually high doses such as 400-960 mg/day of diltiazem sometimes needed for symptom relief 1
- Nitrates (Class IIa, Level B) 1
- Nicorandil as additional option 1
- Combination medical therapy (Class IIb, Level B) is often necessary 1
Prognostic Considerations
Do not underestimate the risk of non-obstructive CAD. Research demonstrates that patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have significantly elevated risks compared to reference populations without ischemic heart disease, with hazard ratios of 1.52 for MACE in those with normal coronaries and 1.85 in those with diffuse non-obstructive disease 4. This underscores why aggressive risk factor modification and mechanism-targeted therapy are essential, not optional.
Monitoring and Follow-Up
- Periodic cardiovascular healthcare visits to reassess risk status, lifestyle modifications, adherence to risk factor targets, and development of comorbidities 2, 3
- Regular monitoring of symptoms, medication adherence, and risk factor control 2, 3
- Multidisciplinary involvement including cardiologists, general practitioners, nurses, dieticians, physiotherapists, psychologists, and pharmacists improves outcomes 2, 3
Knowledge Gaps and Limitations
The 2024 ESC guidelines acknowledge that benefits of antithrombotic therapy in non-obstructive CAD remain uncertain, and current treatments are still largely empirical despite the mechanism-based approach 1. Adjunctive non-pharmacologic treatments including neuromodulation, therapeutic angiogenesis, and coronary sinus reducer therapy require further study 1.