title: Ranolazine: new drug. Stable angina: not worth the risk.
abstract: (1) Betablockers such as atenolol are the first-line symptomatic treatment for stable angina. Calcium channel blockers such as verapamil and amlodipine are second-line alternatives; (2) Ranolazine is now authorized for symptomatic adjuvant treatment of angina in patients who are poorly controlled by a betablocker and/or a calcium channel blocker. Its mechanism of action is poorly understood; (3) In two randomised double-blind trials in respectively 565 and 823 patients treated for 7 and 12 weeks, ranolazine (500 mg to 1000 mg twice a day), added to ongoing amlodipine therapy only provided a limited benefit, preventing less than one angina attack per week; (4) Comparative trials failed to show whether ranolazine has a clear-cut impact on mortality; (5) Ranolazine prolongs the QT interval in a dose-dependent manner and thus exposes patients to the risk of torsades de pointes. It is also associated with gastrointestinal disorders (constipation, nausea, vomiting) and dizziness; (6) Ranolazine is metabolised by the cytochrome P450 isoenzymes CYP 3A4 and CYP 2D6 and is also a P-glycoprotein substrate. There is therefore a high risk of pharmacokinetic interactions. There is also a risk of pharmacodynamic interactions with drugs that prolong the QT interval; (7) In practice, the efficacy of ranolazine in the prevention of angina attacks does not outweigh the risk of severe adverse effects.
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000787:Angina Pectoris / Q000188:drug therapy*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D017277:Drug Approval; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005060:Europe; D006801:Humans; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000069458:Ranolazine
chemical_list: D000083:Acetanilides; D004791:Enzyme Inhibitors; D010879:Piperazines; D000069458:Ranolazine