Management Options in Chronic Stable Angina Pectoris: Focus on Ranolazine

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.