From the Guidelines
Ranolazine (Ranexa) works primarily by inhibiting the late sodium current in cardiac cells, which reduces calcium overload within the cells and leads to improved diastolic relaxation and reduced myocardial oxygen demand. This mechanism differs from traditional anti-anginal medications, as it does not significantly affect heart rate, blood pressure, or contractility 1. By blocking the late sodium current, ranolazine prevents excess sodium from entering cardiac cells during prolonged depolarization, which in turn reduces calcium overload within the cells. This decreased intracellular calcium leads to improved diastolic relaxation and reduced myocardial oxygen demand. Additionally, ranolazine has mild inhibitory effects on fatty acid oxidation, shifting cardiac metabolism toward more oxygen-efficient glucose utilization.
The most recent and highest quality study, published in 2024, supports the use of ranolazine as an 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. The study highlights the importance of considering ranolazine as a second-line treatment to reduce angina frequency and improve exercise tolerance in subjects who cannot tolerate, have contraindications to, or whose symptoms are not adequately controlled by beta-blockers, calcium channel blockers, and long-acting nitrates.
Some key points to consider when using ranolazine include:
- Ranolazine is particularly useful for chronic angina patients who remain symptomatic despite other anti-anginal therapies.
- Ranolazine's unique mechanism allows it to be effective without the hemodynamic effects seen with beta-blockers, calcium channel blockers, or nitrates, making it valuable for patients who cannot tolerate these traditional therapies due to hypotension or bradycardia.
- Ranolazine has a good safety profile, being devoid of any adverse hemodynamic effects when used as monotherapy or in combination 1.
- The recommended initial dose is 500 mg orally twice daily, which can be uptitrated to a maximum of 1000 mg orally twice daily 1.
Overall, ranolazine is a valuable treatment option for patients with chronic angina, particularly those who cannot tolerate traditional anti-anginal therapies. Its unique mechanism of action and good safety profile make it an attractive option for patients who require additional treatment to control their symptoms.
From the FDA Drug Label
- 1 Mechanism of Action
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 QT prolongation effect of ranolazine on the surface electrocardiogram is the result of inhibition of I Kr, which prolongs the ventricular action potential.
The mechanism of action of ranolazine is not fully determined, but it is known to have anti-ischemic and antianginal effects that do not depend on reductions in heart rate or blood pressure. Ranolazine can inhibit the cardiac late sodium current (I Na), but the relationship of this inhibition to angina symptoms is uncertain. The QT prolongation effect of ranolazine is due to inhibition of I Kr, which prolongs the ventricular action potential 2.
From the Research
Mechanism of Action of Ranexa
- Ranexa (ranolazine) has a novel mechanism of action that involves inhibiting the late sodium current in cardiac myocytes, thereby reducing sodium and calcium overload that follows ischemia 3, 4.
- This reduction in sodium and calcium overload improves myocardial relaxation and reduces left ventricular diastolic stiffness, which in turn enhances myocardial contractility and perfusion 3.
- The exact mechanism of action of ranolazine is not fully understood, but it is thought to work by inhibiting the late sodium current, which reduces Na influx and ameliorates disturbed Na and Ca homeostasis 4.
- Ranolazine does not appear to affect either heart rate or blood pressure, making it a useful option for patients with chronic stable angina 3, 5, 6.
Key Effects of Ranexa
- Ranexa reduces the sodium-dependent calcium overload by inhibiting the late sodium current, which leads to a decrease in myocardial oxygen consumption and anginal symptoms 6.
- The drug has been shown to be an effective antianginal and anti-ischemic agent, with a clear clinical benefit achieved in target groups 3, 5.
- Ranexa also has potential antiarrhythmic effects, beneficial effects in diastolic heart failure, and under hyperglycemic conditions 4, 6.