What is the role of Ranolazine in treating chronic angina?

Role of Ranolazine in Treating Chronic Angina

Ranolazine is indicated as an add-on therapy for patients with chronic angina whose symptoms are inadequately controlled with standard antianginal medications such as beta-blockers, calcium channel blockers, or nitrates. 1, 2

Mechanism of Action

Ranolazine works through a unique mechanism compared to traditional antianginal drugs:

• Inhibits the late sodium current (INa), preventing pathologic intracellular calcium accumulation that leads to ischemia 3
• Unlike traditional antianginals, it does not significantly affect heart rate or blood pressure 2
• May improve glucose metabolism under ischemic conditions 2

Clinical Efficacy

Ranolazine has demonstrated efficacy in several key areas:

• Provides modest but statistically significant improvements in exercise duration 4
• Reduces frequency of angina episodes and nitroglycerin consumption 4
• Effective as adjunctive therapy when symptoms are not adequately controlled with standard treatments 1

Dosing and Administration

• Starting dose: 500 mg orally twice daily 5, 1
• Can be titrated up to 1000 mg twice daily based on clinical response 5, 1
• Can be taken with or without meals 1
• Tablets should be swallowed whole, not crushed or chewed 1

Place in Therapy

Ranolazine should be considered in the following scenarios:

1. As add-on therapy: When symptoms persist despite treatment with beta-blockers, calcium channel blockers, or nitrates 1

2. For patients with contraindications to first-line agents: Particularly useful in patients with:

   • Bradycardia or hypotension (due to neutral hemodynamic effects) 3
   • Diabetes mellitus (may improve glycemic control) 2
   • Left ventricular systolic dysfunction (LVEF <40%) 5

3. For patients with microvascular angina: May be effective based on its mechanism of action 2

Special Populations

• Diabetes: Ranolazine should be the preferred approach for patients with diabetes and chronic stable angina due to its favorable effects on glycated hemoglobin levels 2

• Chronic kidney disease: Not recommended when glomerular filtration rate is <30 ml/min/1.73 m² 2

• Chronic obstructive pulmonary disease: Can be considered when beta-blockers are contraindicated 2

Important Precautions

• QT interval prolongation: Ranolazine prolongs the QTc interval in a dose-related manner 1
• Contraindicated in patients taking strong CYP3A inhibitors or inducers 1
• Contraindicated in patients with liver cirrhosis 1
• Dose adjustment (maximum 500 mg twice daily) needed with moderate CYP3A inhibitors such as diltiazem, verapamil, and erythromycin 1

Common Side Effects

• Dizziness
• Nausea
• Constipation
• Headache
• Asthenia (weakness) 4

Clinical Pearls

1. Ranolazine does not improve major cardiovascular outcomes or mortality in patients with chronic stable angina 2

2. Consider ranolazine as a first-choice add-on therapy in patients with diabetes due to its positive metabolic effects 2

3. The neutral hemodynamic profile makes ranolazine particularly valuable for patients who cannot tolerate the bradycardic or hypotensive effects of traditional antianginals 3

4. While ranolazine prolongs the QT interval, clinical evidence suggests it may actually have antiarrhythmic properties 3

5. Set realistic expectations with patients about symptom improvement, as benefits are modest but significant 5