From the Guidelines
Ranolazine works primarily by inhibiting the late sodium current (late INa) in cardiac cells, which reduces intracellular sodium levels and subsequently decreases calcium overload in cardiac myocytes through the sodium-calcium exchanger, thereby improving diastolic relaxation and reducing myocardial oxygen demand. This mechanism of action is supported by the most recent and highest quality study available, which was published in 2018 in the journal Nature Reviews Cardiology 1. The study explains that ranolazine's inhibition of the late sodium current leads to a reduction in calcium overload, which improves diastolic relaxation and reduces myocardial oxygen demand, particularly in ischemic areas of the heart.
Some key points about ranolazine's mechanism of action and effects include:
- Inhibition of the late sodium current reduces intracellular sodium levels, which in turn decreases calcium overload in cardiac myocytes through the sodium-calcium exchanger.
- This reduction in calcium overload improves diastolic relaxation and reduces myocardial oxygen demand, particularly in ischemic areas of the heart.
- Ranolazine's effects on myocardial oxygen demand are achieved without significantly affecting heart rate or blood pressure, making it a useful option for patients who cannot tolerate traditional anti-anginal medications.
- Ranolazine may also have minor effects on fatty acid oxidation and some antiarrhythmic properties due to its effects on various ion channels, as noted in other studies 1.
The typical dosing of ranolazine is 500 mg twice daily initially, which can be increased to 1000 mg twice daily as needed for symptom control, as recommended in the guidelines and supported by the evidence 1. Overall, ranolazine's unique mechanism of action and effects make it a valuable treatment option for patients with angina, particularly those who have not responded to traditional 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 determined. It has anti-ischemic and antianginal effects that do not depend on reductions in heart rate or blood pressure. Ranolazine may inhibit the cardiac late sodium current (I Na), but the relationship of this inhibition to angina symptoms is uncertain 2.
From the Research
Mechanism of Action of Ranolazine
The mechanism of action of ranolazine, an antianginal medicine, is distinct from traditional anti-anginal agents such as beta-blockers and nitrates. Key aspects of its mechanism include:
- Inhibition of the late sodium current (I(Na)) of the cardiac action potential, which reduces myocardial cellular sodium and calcium overload 3, 4, 5, 6.
- Reduction of sodium and calcium accumulation during ischemia, improving myocardial relaxation and reducing left ventricular diastolic stiffness 4, 5.
- Enhancement of myocardial contractility and perfusion without affecting heart rate or blood pressure 3, 4, 5.
Effects of Ranolazine
Ranolazine has been shown to:
- Improve exercise tolerance and reduce ischemic symptoms in patients with chronic angina 3, 4, 5.
- Have pleiotropic effects, including potential benefits on glycemic control, atrial fibrillation, ventricular arrhythmias, diastolic and microvascular dysfunction, and pulmonary arterial hypertension 7, 6.
- Be a favored choice among other anti-anginal agents for patients with comorbidity of chronic angina and diabetes mellitus due to its potential antihyperglycemic effect 7.