Ranolazine
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ADIS DRUG EVALUATION
Ranolazine A Review of Its Use as Add-On Therapy in Patients with Chronic Stable Angina Pectoris Gillian M. Keating
Published online: 11 January 2013 Ó Springer International Publishing Switzerland 2013
Abstract Extended-release ranolazine (ranolazine ER) [RanexaÒ] is an antianginal agent that achieves its effects via a novel mechanism of action (inhibition of the late phase of the inward sodium current), without affecting heart rate or blood pressure (BP). This article reviews the efficacy, safety and tolerability of ranolazine ER as add-on therapy in patients with chronic stable angina pectoris, as well as summarizing its pharmacological properties and its use in non-ST-elevation acute coronary syndromes. In the CARISA and ERICA trials, add-on therapy with ranolazine ER improved exercise tolerance and/or reduced angina frequency and nitroglycerin use in patients with chronic stable angina; benefits were seen across a variety of patient subgroups. Although results of the MERLIN-TIMI 36 trial do not support the use of ranolazine ER in the acute management of non-ST-elevation acute coronary syndromes, they do support its use as an antianginal therapy. Ranolazine ER was generally well tolerated, with the most commonly reported adverse events including dizziness, nausea, asthenia and constipation. Despite being associated with modest increases in the corrected QT interval, ranolazine ER demonstrated antiarrhythmic effects in the MERLIN-TIMI 36 trial. In conclusion, ranolazine ER The manuscript was reviewed by: N. Fragakis, Third Cardiology Department, Hippokration Hospital, Aristotle University Medical School, Thessaloniki, Greece; V. Pasceri, Emodinamica, Ospedale San Filippo Neri, Rome, Italy; F. Pelliccia, Department of Heart and Great Vessels Attilio Reale, La Sapienza University, Rome, Italy; H. Purcell, Royal Brompton Hospital, Department of Cardiology, London, UK; S. Sossalla, Department of Cardiology & Pneumology, Georg-August-University, Go¨ttingen, Germany. G. M. Keating (&) Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand e-mail: [email protected]
provides an important option for use as add-on therapy to reduce symptoms in patients with chronic stable angina.
1 Introduction Chronic stable angina pectoris is a common condition in industrialized countries such as the USA and countries in Western Europe [1]. The incidence of chronic stable angina is expected to increase in the future, in part as a result of the aging of the population [1]. Despite the aggressive use of conventional antianginal therapies, many patients experience persistent angina. For example, in the COURAGE trial, &25 % of patients still experienced angina at 5 years despite receiving optimal medical therapy (i.e. long-acting metoprolol, amlodipine and isosorbide mononitrate, alone or in combination) with or without percutaneous coronary intervention (PCI) [2]. Thus, there is a need for additional antianginal agents with novel mechanisms of action. Ranolazine is one such ant
