Ranolazine for Microvascular Angina
Ranolazine can be considered as add-on therapy for microvascular angina when symptoms remain inadequately controlled on standard antianginal medications, though the evidence shows mixed results with symptom improvement but no clear benefit on objective ischemia measures. 1, 2
Guideline Recommendations
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 recommendation). 1, 2 This recommendation applies to microvascular angina patients specifically, recognizing the unique pathophysiology of this condition. 2
Evidence Quality and Limitations
The evidence for ranolazine in microvascular angina is notably weaker than for obstructive coronary disease:
A larger trial in microvascular angina patients did not show superiority of ranolazine compared with placebo on the frequency of angina or reduction in myocardial ischemia evaluated by single-photon emission computed tomography. 3 This is the most definitive evidence available and suggests limited objective benefit.
Smaller studies have shown more promising results, with one randomized trial demonstrating improvements in Seattle Angina Questionnaire scores and exercise tolerance compared to placebo in MVA patients. 4 Another observational study showed 80.6% of patients experienced quality of life improvements and reduced healthcare system interactions. 5
Individual case reports document complete symptom resolution and improved coronary flow reserve with ranolazine treatment. 6
Mechanism Supporting Use in Microvascular Disease
Ranolazine's mechanism is theoretically well-suited for microvascular angina:
It inhibits the late sodium current, preventing intracellular calcium overload during ischemia—a key pathophysiologic mechanism in microvascular dysfunction. 1, 2
It reduces sodium-dependent intracellular calcium accumulation, leading to decreased oxygen demand and improved diastolic relaxation, which enhances myocardial perfusion. 2, 6
Critically, ranolazine does not significantly affect heart rate or blood pressure, making it particularly useful when other antianginal agents are limited by bradycardia or hypotension. 1, 2
Ideal Patient Selection
Ranolazine is most appropriate for microvascular angina patients with:
- Bradycardia or hypotension preventing use of beta-blockers or calcium channel blockers 1, 2
- Diabetes mellitus, as ranolazine reduces HbA1c levels (though not indicated as diabetes treatment) 3, 1
- Left ventricular hypertrophy, where ranolazine may be more effective than other agents 3, 1
- Persistent symptoms despite maximal standard therapy 2, 5
Dosing and Administration
Start ranolazine at 500 mg orally twice daily, escalating as needed to a maximum of 1000 mg twice daily. 1 Assess symptom response after at least 6 weeks of treatment. 5
Critical Contraindications and Precautions
Absolutely contraindicated in hepatic impairment or liver cirrhosis due to dose-dependent QT prolongation risk. 3, 1, 2
Causes dose-related QTc prolongation, though torsades de pointes has not been observed at therapeutic doses. 1
Increases digoxin concentrations—use with caution if co-administered. 3, 1, 2
Clinical Reality
Despite theoretical benefits and some positive symptom data, ranolazine does not improve hard cardiovascular outcomes (death, myocardial infarction) in chronic stable angina patients. 3, 1 The disconnect between symptom improvement in smaller studies and lack of objective ischemia reduction in the larger trial suggests ranolazine's benefit in microvascular angina may be primarily symptomatic rather than disease-modifying. 3 Given the benign safety profile and lack of hemodynamic effects, a trial of ranolazine is reasonable in symptomatic patients who have exhausted other options, particularly those with the favorable characteristics listed above. 2, 5