Clinical Medicine: Therapeutics
Synopsis: An open access, peer reviewed electronic journal that covers therapeutics in human clinical medicine.
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Management Options in Chronic Stable Angina Pectoris: Focus on Ranolazine
Authors: David S. Vadnais and Nanette K. Wenger
Publication Date: 31 Jul 2009
Clinical Medicine: Therapeutics 2009:1 871-887
David S. Vadnais1 and Nanette K. Wenger2
1Chief Cardiovascular Fellow, Emory University Hospital, Atlanta, GA, USA. 2Professor of Medicine (Cardiology), Emory University School of Medicine, Chief of Cardiology, Grady Memorial Hospital, Consultant Emory Heart and Vascular Center, Atlanta, GA, USA.
Abstract
Chronic stable angina pectoris results from a fixed coronary arterial obstruction causing an imbalance between myocardial oxygen supply and demand. Current therapy aims to reduce cardiovascular events (vasculoprotective) thereby improving survival, and/or relieve ischemic symptoms (antianginal) thereby improving the quality of life. Vasculoprotective therapy consists of lifestyle modification, antiplatelet agents, lipid lowering therapy and angiotensin-converting enzyme (ACE) inhibitors. Conventional antianginal therapy for patients with chronic stable angina consists of beta-blockers, calcium channel blockers and nitrates, with surgical or percutaneous revascularization serving an adjunctive role. Despite the investigation of multiple novel therapies and medications over the past 25 years, arguably the most significant contribution to antianginal therapy during that time involved the recent introduction of ranolazine. Ranolazine acts via a distinctive pathway, inhibiting the late sodium current of the action potential in ischemic myocytes. Multiple studies have demonstrated that ranolazine significantly reduces anginal symptoms and improves exercise performance in patients with chronic stable angina but does not reduce mortality. Ranolazine does not affect either heart rate or blood pressure, a unique property among the current antianginal agents. Despite its QT prolongation, ranolazine has a proven safety profile and is not proarrhythmic. In fact, in a recent large randomized trial, ranolazine reduced the incidence of supraventricular tachycardia, ventricular tachycardia, new-onset atrial fibrillation and bradycardic events. Ranolazine may confer some additional benefits such as a reduction in HbA1c levels and improved left ventricular diastolic function. Ranolazine is now approved for use in chronic stable angina. Current guidelines recommend beta-blockers as the first line antianginal agent due to the proven mortality reduction. However, for patients with bradycardia or hypotension, ranolazine may be considered as initial antianginal therapy.
Keywords: chronic angina, myocardial ischemia, ranolazine, pharmacotherapy, antianginal, sodium current
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Modifications of Antiepileptic Drugs for Improved Tolerability and Efficacy - 14/Feb/2008
Exploratory Studies on Development of the Chemokine Receptor CXCR4 Antagonists Toward Downsizing - 10/Feb/2008
The Role of Glucose Metabolism and Glucose-Associated Signalling in Cancer - 18/Jan/2008
Chemical Chaperone and Inhibitor Discovery: Potential Treatments for Protein Conformational Diseases - 11/Dec/2007
Derivatives of 5-Aminolevulinic Acid for Photodynamic Therapy - 11/Dec/2007
The pKa Distribution of Drugs: Application to Drug Discovery - 17/Sep/2007