Ranolazine for the management of coronary artery disease

Despite coronary revascularization and standard antianginal therapy, many patients continue to experience symptoms of stable angina and progression of their disease. Ranolazine is a new class of antianginal agent. Unlike standard antianginal agents, it alters glucose and fatty acid metabolism for a different approach to the management of coronary artery disease. This article discusses the clinical pharmacology of ranolazine and its use in the management of chronic stable angina. Peer-reviewed articles and abstracts were identified from MEDLINE and the Current Contents database (both from 1966 to September 20, 2006) using the search terms ranolazine, angina, pharmacokinetics, and pharmacology. Citations from available articles were reviewed for additional references. Abstracts presented at recent professional meetings were also reviewed. Ranolazine is a cell membrane inhibitor of the late sodium current. Extended-release ranolazine was recently approved in the United States for the treatment of chronic angina. Ranolazine is metabolized in the liver by the cytochrome P-450 (CYP) 3A4 system. Because of its potential to prolong corrected QT (QTc) intervals, ranolazine should not be used in patients with hepatic impairment, those with QTc prolongation, or those taking drugs known to prolong QTc intervals or drugs that are potent CYP 3A4 inhibitors. Other adverse effects of ranolazine include dizziness, headache, constipation, and nausea. Placebo-controlled clinical studies performed to date have found that sustained-release ranolazine 500 to 1500 mg PO BID was associated with significantly increased time to onset of angina (range of increase, 27.0–144.0 s; P < 0.05 [varied among studies]), exercise duration (range of increase, 23.8–99.0 s; P < 0.05 [varied among studies] ), and time to 1-mm ST depression (range of increase, 27.6–146.2 s; P < 0.05 [varied among studies]). In addition, exercise duration was found to be significantly longer with ranolazine compared with atenolol (453 vs 430 s; P = 0.006). Ranolazine is a new antianginal agent that is effective in the management of chronic angina. Its unique mechanism of action warrants further study in other cardiovascular conditions such as heart failure and arrhythmias. Ongoing studies will address whether ranolazine can reduce clinical end points such as cardiovascular death and myocardial infarction.