Treatment Recommendations for Coronary Microvascular Dysfunction

First-Line Pharmacological Strategy

The European Society of Cardiology recommends statins as mandatory in all patients with coronary microvascular dysfunction (CMD), as they improve coronary endothelial function, microvascular function, and reduce inflammation 1, 2, 3
If lipid goals are not achieved with maximum tolerated statin dose, the European Society of Cardiology suggests adding ezetimibe 1, 2, 3
For very high-risk patients not reaching goals on statin plus ezetimibe, the European Society of Cardiology recommends adding a PCSK9 inhibitor 1, 2, 3
ACE inhibitors (or ARBs if ACE-I intolerant) are essential for treating microvascular endothelial dysfunction, particularly when hypertension, diabetes, or heart failure coexist 1, 2, 3
Beta-blockers and/or calcium channel blockers are first-line for controlling heart rate and angina symptoms 1, 2, 3
Short-acting nitrates are recommended for immediate relief of effort angina 1, 2, 3
The European Society of Cardiology advises avoiding nitrates in patients with hypertrophic obstructive cardiomyopathy or those taking phosphodiesterase inhibitors 3

The European Society of Cardiology recommends low-dose aspirin (75-100 mg daily) for patients with previous MI or revascularization 1, 2, 3
Clopidogrel 75 mg daily is suggested as an alternative if aspirin is intolerant 1, 2, 3
The European Society of Cardiology recommends adding a proton pump inhibitor if there is a high gastrointestinal bleeding risk 1, 2, 3

Invasive coronary functional testing provides definitive diagnosis and guides stratified therapy 4
CFR <2.5 indicates CMD (measured by thermodilution or Doppler) 4
IMR ≥25 or HMR >2.5 mmHg/cm/s confirms microvascular dysfunction 4
Acetylcholine testing identifies endothelial-dependent dysfunction and vasospasm 4

Functional CMD (62% of CMD cases): Normal minimal microvascular resistance (hyperemic MR <2.5 mmHg/cm/s) with lower resting MR (4.2±1.0 mmHg/cm/s), characterized by enhanced nitric oxide synthase activity and increased resting flow 4
Structural CMD (38% of CMD cases): Elevated hyperemic MR (≥2.5 mmHg/cm/s) with higher resting MR (6.9±1.7 mmHg/cm/s) and greater systolic blood pressure response during exercise (188±25 mmHg), indicating endothelial dysfunction with reduced exercise flow augmentation 4

Lifestyle modification is mandatory: smoking cessation, nutrition counseling, and structured physical activity 1, 2, 3
The European Society of Cardiology recommends exercise-based cardiac rehabilitation as fundamental 5
Multidisciplinary team involvement (cardiologists, primary care, nurses, dieticians, physiotherapists, psychologists, pharmacists) is recommended 1, 2, 3
Psychological interventions for depression symptoms are suggested 1, 2, 3
Annual influenza vaccination is recommended, especially in elderly patients 3
Aggressive management of hypertension, diabetes, anemia, and obesity is advised 1, 2

CMD is not benign: Annual adverse cardiac event risk is 2.5%, including MI, stroke, heart failure, and death 4
The European Society of Cardiology recommends reviewing treatment response at 2-4 weeks after drug initiation to ensure adequate symptom control and medication tolerance 3