Emerging clinical role of ranolazine in the management of angina

Chronic stable angina is an exceedingly prevalent condition with tremendous clinical, social, and financial implications. Traditional medical therapy for angina consists of beta-blockers, calcium channel blockers, and nitrates. These agents decrease myocardial oxygen demand and ischemia by reducing heart rate, lowering blood pressure, and/or optimizing ventricular loading characteristics. Unique in its mechanism of action, ranolazine is the first new antianginal agent approved for use in the US for chronic angina in over 25 years. By inhibiting the late inward sodium current (I(Na)), ranolazine prevents pathologic intracellular calcium accumulation that leads to ischemia, myocardial dysfunction, and electrical instability. Ranolazine has been proven in multiple clinical trials to reduce the symptoms of angina safely and effectively and to improve exercise tolerance in patients with symptomatic coronary heart disease. These benefits occur without reduction in heart rate and blood pressure or increased mortality. Although ranolazine prolongs the QT(c), experimental data indicate that ranolazine may actually be antiarrhythmic. In a large acute coronary syndrome clinical trial, ranolazine reduced the incidence of supraventricular tachycardia, ventricular tachycardia, new-onset atrial fibrillation, and bradycardic events. Additional benefits of ranolazine under investigation include reductions in glycosylated hemoglobin levels and improved left ventricular function. Ranolazine is a proven antianginal medication in patients with symptomatic coronary heart disease, and should be considered as an initial antianginal agent for those with hypotension or bradycardia.