Ranolazine (Ranexa): A First-in-Class Therapy for Stable Angina

488 P&T® • September 2007 • Vol. 32 No. 9 INTRODUCTION Angina pectoris (chest pain) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arm. It occurs when the myocardial demand for oxygen (MVO2) exceeds the oxygen supply, leading to myocardial ische mia. Typically, angina is the result of coronary artery disease (CAD), also known as ischemic heart disease (IHD) and coronary heart disease (CHD). CHD remains the single leading cause of death in the U.S., afflicting 13.2 million Americans and accounting for 20% of all deaths. Approximately 6.5 million people in the U.S. experience angina, with 400,000 new cases of stable angina emerging annually in the U.S. Stable angina typically occurs with physical exertion or emotional stress and is relieved by rest, nitroglycerin, or both. It is often predictable and reproducible, typically lasting for several minutes. Unstable angina, which falls under the umbrella term of acute coronary syndrome (ACS), occurs at rest, is characterized by a longer duration, and is often more painful than stable angina. Most cases of CHD are caused by atherosclerosis of the epicardial vessels. In addition to stable and unstable angina, other manifestations of atherosclerosis include heart failure, myocardial infarction (MI), stroke, peripheral arterial disease , and arrhythmias. Several risk factors can predispose patients to CHD and lead to its progression: smoking, diabetes, hypertension, hyperlipidemia, obesity, and a sedentary lifestyle. Appropriate identification and treatment of CHD risk factors play a crucial role in the management of CHD (Figure 1). Treatment goals for patients with stable angina are to reduce the risk of mortality and morbid events, such as MI, arrhy thmias, and heart failure. Treatment is also aimed at reducing or elim inating angina symptoms, thereby improving patients’ quality of life and increasing their exercise capability. Until recently, three major classes of anti-ischemic drugs were available for the medical management of chronic stable angina: nitrates, beta blockers, and calcium-channel blockers (CCBs). Some patients may require a procedure in addi tion to medical therapy, such as percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). Episodes of chronic stable angina are typically precipitated by an increase in MVO2 in the setting of a fixed decrease in the oxygen supply. This decrease is a result of atherosclerotic plaque formation and progression of CAD. The major determinants of MVO2 are heart rate, intramyoc ardial wall tension, and myo cardial contractility. Antianginal drugs exhibit their effects by reducing the dif feren t components of MVO2. Current practice guidelines recommend the use of a beta blocker as a first-line anti-ischemic therapy in the absence of contraindications (Table 1). CCBs or long-acting nitrates may be used when a beta blocker is contraindicated, or they may be used in combination with a beta blocker if suboptimal results are achieved with initial betablocker treatment. Despite the use of traditional anti anginal agents and revascularization procedures, anginal episodes still occur. These episodes, in turn, can decrease patients’ quality of life by limiting their functional independence and their ability to perform daily physical activities. Many patients, par ticularly in the elderly age group, have relative intolerance to full doses of these agents (see Table 1). On January 27, 2006, the Food and Drug Administration (FDA) approved extended-release ranolazine (Ranexa, CV Therapeutics) as a new molecular entity in the U.S. for patients with chronic angina who continue to be symptomatic after beta-blocker, CCB, or nitrate therapy. It is the first drug in more than 10 years that has been approve d to treat chronic angina.