Ranolazine Topic Review

Ranolazine is an antianginal drug and a class V antiarrhythmic drug that is mainly used for the treatment of chronic angina.

Ranolazine is also used off-label to treat certain arrhythmias, including ventricular tachycardia. [Reed M, et al. StatPearls [Internet]. 2023]

The drug inhibits the late phase of inward sodium channels in ischemic cardiac myocytes, reducing the intracellular sodium concentration and reducing intracellular calcium influx via the sodium/calcium channel, which reduces ventricular wall tension and oxygen consumption. It has little effect on heart rate and blood pressure. [Reed M, et al. StatPearls [Internet]. 2023]

Notable adverse effects of ranolazine include bradycardia, hypotension, headache, dizziness, syncope, nausea and dyspnea. [Al-Khatib SA, et al. J Am Coll Cardiol. 2017;e114f]

In the 2023 American College of Cardiology/American Heart Association/Multisociety Guideline for the Management of Patients with Chronic Coronary Disease, ranolazine is recommended (Class 1 recommendation) in patients with chronic coronary disease who continue to have angina symptoms despite treatment with beta-blockers, calcium channel blockers or long-acting nitrates. [Virani SA, et al. J Am Coll Cardiol. 2023;889a]

The guideline also identifies ranolazine as a third-line therapy option in patients with microvascular angina, defined as proven coronary microvascular disease but no obstructive coronary artery disease. [Virani SA, et al. J Am Coll Cardiol. 2023;899c]

In the overall results of the MERLIN-TIMI 36 trial of ranolazine compared with placebo for patients with acute coronary syndrome, ranolazine was not superior to placebo for reduction of cardiovascular (CV) death, myocardial infarction (MI) and recurrent ischemia. However, ranolazine was superior to placebo for reduction of CV death, MI and recurrent ischemia, driven by lower recurrent ischemia, in a post hoc analysis that included only women, and was superior to placebo for reduction of CV death, MI and recurrent ischemia, as well as for reduction of worsening angina and increase of exercise duration, in a subgroup analysis including only patients with prior chronic angina. [Amsterdam EA, et al. Circulation. 2014;e363a]

Because it shortens the corrected QT interval, ranolazine has been used to reduce recurrent arrhythmias in patients with long QT syndrome type 3. [Al-Khatib SA, et al. J Am Coll Cardiol. 2017;e153a]

References:

• Al-Khatib SM, et al. J Am Coll Cardiol. 2017;doi:10.1016/j.jacc.2017.01.054.

• Amsterdam EA, et al. Circulation. 2014;doi:10.1161/CIR.0000000000000134.

• Reed M, et al. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK507828. Updated May 16, 2023. Accessed May 1, 2024.

• Virani SA, et al. J Am Coll Cardiol. 2023;doi:10.1016/j.jacc.2023.04.003.