Ranolazine for Coronary Microvascular Dysfunction (CMD)

Introduction to Ranolazine Therapy

• The European Society of Cardiology recommends ranolazine as add-on therapy in patients with inadequate symptom control while on beta-blockers and/or calcium channel blockers, or as part of initial treatment in properly selected patients (Class IIa, Level B) 1, 2

Mechanism of Action and Clinical Evidence

• Ranolazine works through inhibition of the late sodium current (late INa), which prevents intracellular calcium overload during ischemia—a key pathophysiologic mechanism in microvascular dysfunction, without significantly affecting heart rate or blood pressure 3, 2
• The drug reduces sodium-dependent intracellular calcium accumulation during ischemia, leading to decreased oxygen demand and left ventricular wall tension 3

Guideline Recommendations and Patient Selection

• The European Society of Cardiology guidelines recommend ranolazine as add-on therapy in patients with inadequate symptom control while on beta-blockers and/or calcium channel blockers, or as part of initial treatment in properly selected patients (Class IIa, Level B) 1, 2
• Ideal candidates for ranolazine in CMD include patients with bradycardia or hypotension who cannot tolerate rate-lowering or blood pressure-lowering agents, diabetic patients with CMD, patients with left ventricular hypertrophy, and those with more severe CMD 2, 3

Safety and Contraindications

• Ranolazine is contraindicated in patients with liver cirrhosis or hepatic impairment 3, 2
• Safety considerations include dose-related QTc prolongation, use caution with strong CYP3A inhibitors, and increases digoxin concentrations—use caution if co-administered 3, 2