From the Guidelines
Ranolazine is an antianginal medication that works through a unique mechanism of action, primarily functioning as a selective inhibitor of the late sodium current in cardiac cells, making it particularly useful for chronic stable angina patients. The mechanism of action of ranolazine involves inhibiting the late inward sodium current, which reduces the deleterious effects of intracellular sodium and calcium overload that accompany myocardial ischemia 1. This is further supported by a more recent study that highlights ranolazine's ability to promote glucose oxidation and improve anaerobic metabolism under ischemic conditions, in addition to its effects on the late sodium current 1. The most recent guideline recommends long-acting nitrates or ranolazine as add-on therapy in patients with inadequate control of symptoms while on treatment with beta-blockers and/or calcium channel blockers, or as part of initial treatment in properly selected patients 1. Key points to consider when prescribing ranolazine include:
- Starting dose of 500 mg twice daily, which can be increased to 1000 mg twice daily as needed
- Availability as extended-release tablets, which can be taken with or without food
- Potential for QT prolongation, requiring caution in patients with existing QT prolongation or those taking other QT-prolonging medications
- Efficacy in reducing symptoms of chronic stable angina, similar to other antianginal agents, without significantly affecting heart rate, blood pressure, or contractility 1. Overall, ranolazine's unique mechanism of action and favorable safety profile make it a valuable option for the treatment of chronic stable angina, particularly in patients who remain symptomatic despite other antianginal therapies.
From the FDA Drug Label
The mechanism of action of ranolazine’s antianginal effects has not been determined. Ranolazine has anti-ischemic and antianginal effects that do not depend upon reductions in heart rate or blood pressure. It does not affect the rate-pressure product, a measure of myocardial work, at maximal exercise Ranolazine at therapeutic levels can inhibit the cardiac late sodium current (I Na). However, the relationship of this inhibition to angina symptoms is uncertain.
The mechanism of action of ranolazine is not fully understood, but it is known to have anti-ischemic and antianginal effects that do not rely on reducing heart rate or blood pressure. Ranolazine may inhibit the cardiac late sodium current (I Na), but the connection between this inhibition and angina symptoms is unclear 2.
From the Research
Mechanism of Action of Ranolazine
- Ranolazine is a novel antianginal and anti-ischemic agent that works by reducing the sodium-dependent calcium overload, inhibiting the late sodium current 3.
- Its exact mechanism of action is unknown, but it has been shown to increase the electrocardiographic QTc interval in a dose-related manner, without significant proarrhythmic effects at therapeutic doses 4.
- Ranolazine is hemodynamically neutral, exerting its antianginal effect without significantly impacting patient heart rate or blood pressure 5, 6.
Effects of Ranolazine
- Ranolazine has been shown to be effective in reducing anginal symptoms in patients with chronic stable angina, with a safe and tolerable profile 4, 5, 6.
- It has also been found to have favorable effects in decreasing the arrhythmic burden and improving the glycemic profile of patients with chronic coronary syndromes 3.
- Ranolazine treatment is associated with QTc-interval prolongation, but this does not appear to have clinical consequences, and may even have an antiarrhythmic effect in patients 5.
Clinical Use of Ranolazine
- Ranolazine is currently approved for the treatment of angina pectoris, either as monotherapy or added to beta-blockers, nitrates, and calcium channel blockers 4, 6.
- It is not approved for the treatment of unstable angina, silent ischemia, or cardiac arrhythmias 4.
- The most common adverse effects reported in clinical trials during ranolazine treatment are dizziness, headaches, constipation, and nausea 4, 5, 6.