Advances in the Management of Stable Angina

OBJECTIVE: To describe the approved uses, pharmacology, pharmacodynamics, pharmacokinetics, efficacy, safety, and place in therapy of ranolazine, the first new antianginal drug therapy introduced in more than 20 years for the treatment of chronic angina. SUMMARY: The mechanism of action of ranolazine is unknown, but it may involve inhibition of the late sodium current in the myocardium, thereby preventing sodium-induced intracellular calcium overload during ischemia. This mechanism differs from that of other antianginal agents, which primarily affect myocardial oxygen supply or demand through hemodynamic effects. Ranolazine undergoes extensive metabolism, primarily by cytochrome P-450 (CYP) 3A4, so interactions with drugs that are moderate to potent inhibitors of CYP3A4 need to be considered. Ranolazine is also a P-glycoprotein (P-gp) substrate and inhibitor, and it may interact with other P-gp substrates and inhibitors. In patients with an inadequate response to other antianginal agents, the addition of ranolazine to existing antianginal therapy increases exercise duration and the time to angina on an exercise treadmill test, and it decreases the frequency of angina attacks and nitroglycerin use. The drug produces antianginal effects without significantly affecting either heart rate or blood pressure. Ranolazine prolongs the QT interval on the electrocardiogram, but the overall electrophysiologic effects of the drug suggest that it is not expected to cause torsades de pointes. CONCLUSION: Ranolazine has a unique mechanism of action that may be complementary to that of conventional antianginal agents in the treatment of chronic angina. An understanding of the potential for drug interactions, disease interactions, and contraindications is needed to ensure safe and effective use of the drug.