What is the recommended treatment for chronic angina using Ranexa (ranolazine)?

Ranolazine for Chronic Angina Management

Ranolazine should be considered as add-on therapy in patients with inadequate control of chronic angina symptoms while on treatment with beta-blockers and/or calcium channel blockers, or as part of initial treatment in properly selected patients. 1

Indications and Dosing

• Ranolazine is FDA-approved for the treatment of chronic angina and may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers 2
• Initiate ranolazine at 500 mg twice daily and increase to 1000 mg twice daily as needed based on clinical symptoms 2
• Ranolazine should be taken with or without meals, and tablets must be swallowed whole (not crushed, broken, or chewed) 2
• The maximum recommended daily dose is 1000 mg twice daily 2

Mechanism of Action and Clinical Benefits

• Ranolazine works primarily through inhibition of the late sodium current (late INa), which prevents intracellular calcium overload during ischemia 3
• Unlike traditional antianginals, ranolazine exerts its antianginal effects without significantly affecting heart rate or blood pressure, making it particularly useful in patients with bradycardia or hypotension 3, 4
• Clinical trials have demonstrated that ranolazine:
  • Improves exercise duration and time to angina 2
  • Reduces angina frequency and nitroglycerin use 2, 5
  • Does not develop tolerance after 12 weeks of therapy 2

Place in Therapy

• According to the 2024 ESC guidelines, ranolazine should be considered as add-on therapy in patients with inadequate control of symptoms while on treatment with beta-blockers and/or calcium channel blockers (Class IIa, Level B recommendation) 1
• Ranolazine can also be considered as part of initial treatment in properly selected patients 1
• Long-term safety data from the ROLE program showed that ranolazine is well-tolerated in high-risk coronary heart disease patients with 76.7% of patients remaining on therapy after 2 years 6

Special Populations and Considerations

• Patients with diabetes and chronic stable angina may benefit from ranolazine treatment, as it has been shown to reduce glycated hemoglobin levels 1, 3, 7
• Patients with left ventricular hypertrophy might experience greater efficacy with ranolazine compared to other antianginal drugs 1, 4
• Ranolazine may be particularly useful in cases of bradycardia and/or hypotension due to its neutral hemodynamic profile 1, 4, 7

Contraindications and Precautions

• Ranolazine is contraindicated in patients:
  • Taking strong inhibitors of CYP3A 2
  • Taking inducers of CYP3A 2
  • With liver cirrhosis 1, 2
• Dose adjustments are required when ranolazine is taken with moderate CYP3A inhibitors (limit to 500 mg twice daily) 2
• Ranolazine prolongs the QTc interval in a dose-related manner, though clinical trials have not shown an increased risk of proarrhythmia or sudden death 2, 6
• Use with caution in patients taking digoxin, as ranolazine increases digoxin concentration 1

Adverse Effects

• Common adverse effects include dizziness, nausea, asthenia (weakness), constipation, and headache 5, 7
• Despite QTc interval prolongation, ranolazine has not been associated with increased incidence of torsades de pointes at therapeutic doses 6, 7

Clinical Outcomes

• While ranolazine effectively reduces angina symptoms and improves exercise tolerance, it has not been shown to improve major cardiovascular outcomes or reduce mortality in patients with chronic stable angina 1, 5
• The ROLE program showed an annual mortality of 2.8% in high-risk coronary heart disease patients treated with ranolazine, which was lower than predicted by the Duke Treadmill Score 6