Ranolazine in patients with coronary artery disease

Abstract

Traditional anti-anginal agents such as β-blockers and nitrates improve symptoms of cardiac ischemia by affecting either blood pressure or heart rates. Despite aggressive therapy, many patients suffer persistent angina, and optimal therapy is limited by intolerance to traditional agents. Ranolazine, a novel anti-anginal agent that is approved for use in the US, is felt to improve ischemic symptoms by reducing myocardial cellular sodium and calcium overload via inhibition of the late sodium current (I_Na) of the cardiac action potential. Several Phase-III trials in patients with chronic angina have demonstrated that ranolazine improves exercise tolerance and reduces ischemic symptoms as compared with placebo. In the largest evaluation of ranolazine, the MERLIN-TIMI 36 trial (Metabolic Efficiency with Ranolazine for Less Ischemia in non ST elevation acute coronary syndrome), ranolazine did not reduce the risk of death or recurrent myocardial infarction in patients with non-ST-elevation acute coronary syndromes, but it did improve ischemic symptoms over the subsequent year of therapy. Thus, ranolazine offers clinicians a new therapy in the long-term treatment of patients with chronic angina.

Keywords::

• chronic angina
• ischemia
• pharmacotherapy
• ranolazine

Disclosure

The TIMI study group, where Dr Scirica is employed, reports receiving research grant support from Accumetics, Amgen, AstraZeneca, Bayer healthcare, Beckman Coulter, Biosite, Bristol-Myers Squibb, CV Therapeutics, Eli Lilly, GlaxoSmithKline, Inotek Pharmaceuticals, Nuvelo, Ortho-Clinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi-Aventis, Sanofi-Synthelabo and Schering-Plough. In addition, Dr Scirica reports receiving honoraria for educational presentations from CV Therapeutics and sanofi-aventis, serving as a consultant for Chroma Therapeutics and Prolexys, being on the speaker's bureau of Pfizer and being on an advisory board for Novartis. This article was independently commissioned, and no fee was received for preparation of this manuscript.

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