https://doi.org/10.4081/monaldi.2021.1806
Through the heart and beyond: a review on ranolazine
Submitted: February 15, 2021
Accepted: June 25, 2021
Published: September 9, 2021
Accepted: June 25, 2021
Abstract Views: 2138
PDF: 881
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Ranolazine derives from piperazine and has been approved as a drug for the therapy of chronic stable angina. It acts by selectively inhibiting the late sodium inward current. Moreover, ranolazine has other metabolic features which makes it effective in other diseases as well as coronary artery ones. In this paper I make an updated review of all possible therapeutic roles of ranolazine: through cardiology and beyond.
Chaitman BR. Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation 2006;113:2462-72.
Clarke B, Wyatt KM, McCormack JG. Ranolazine increases active pyruvate dehydrogenase in perfused normoxic rat hearts: evidence for an indirect mechanism. J Mol Cell Cardiol 1996;28:341-50.
Le DE, Davis CM, Wei K, et al. Ranolazine may exert its beneficial effects by increasing myocardial adenosine levels. Am J Physiol Heart CircPhysiol 2020;318:H189-H202.
Zhao G, Walsh E, Shryock JC, et al. Antiadrenergic and hemodynamic effects of ranolazine in conscious dogs. J Cardiovasc Pharmacol 2011;57:639-647
Rousseau MF, Pouleur H, Cocco G, Wolff AA. Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris. Am J Cardiol 2005;95:311-6.
Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, et al. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA 2007;297:1775-83.
Antzelevitch C, Belardinelli L, Zygmunt AC, et al. Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation 2004;110:904-10
Schwemer TF, Radziwolek L, Deutscher N, et al. Effect of ranolazine on ischemic myocardium in patients with acute cardiac ischemia (RIMINI-Trial): A randomized controlled pilot trial. J Cardiovasc Pharmacol Ther 2019;24:62-9.
Calcagno S, Infusino F, Salvi N, et al. The role of ranolazine for the treatment of residual angina beyond the percutaneous coronary revascularization. J Clin Med 2020;9:2110.
Uran C, Di Chiara G, Bosco B, et al. A case of vasospastic angina. Vasospasm physiopathology: a new therapeutic role for ranolazine? Monaldi Arch Chest Dis 2020;90:1295.
Ghosh GC, Ghosh RK, Bandyopadhyay D, et al. Ranolazine: Multifaceted role beyond coronary artery disease, a recent perspective. Heart Views 2018;19:88-98.
Nieminen T, Tavares CAM, Pegler JRM, et al. Ranolazine injection into coronary or femoral arteries exerts marked, transient regional vasodilation without systemic hypotension in an intact porcine model. Circ Cardiovasc Interv 2011;4:481-7.
Rayner-Hartley E, Parvand M, Humphries KH, et al. Ranolazine for symptomatic management of microvascular angina. Am J Ther 2020;27:e151-8.
Stone PH. Ranolazine: new paradigm for management of myocardial ischemia, myocardial dysfunction, and arrhythmias. Cardiol Clin 2008;26:603–14.
Minotti G, Menna P, Calabrese V, et al. Pharmacology of ranolazine versus common cardiovascular drugs in patients with early diastolic dysfunction induced by anthracyclines or nonanthracycline chemotherapeutics: A phase 2b minitrial. J Pharmacol Exp Ther 2019;370:197-205.
Maier LS, Layug B, Karwatowska-Prokopczuk E, et al. RAnoLazIne for the treatment of diastolic heart failure in patients with preserved ejection fraction: The RALI-DHF proof-of-concept study. JACC Heart Fail 2013;1:115-22.
Nie J, Duan Q, He M, et al. Ranolazine prevents pressure overload-induced cardiac hypertrophy and heart failure by restoring aberrant Na+ and Ca2+ handling. J Cell Physiol 2019;234:11587-601.
Coppini R, Mazzoni L, Ferrantini C, et al. Ranolazine prevents phenotype development in a mouse model of hypertrophic cardiomyopathy. Circ Heart Fail 2017;10:e003565.
Ferrantini C, Pioner JM, Mazzoni L, et al. Late sodium current inhibitors to treat exercise-induced obstruction in hypertrophic cardiomyopathy: an in vitro study in human myocardium. Br J Pharmacol 2018;175:2635-52.
Olivotto I, Camici PG, Merlini PA, et al. Efficacy of ranolazine in patients with symptomatic hypertrophic cardiomyopathy: The RESTYLE-HCM randomized, double-blind, placebo-controlled study. Circ Heart Fail 2018;11:e004124.
Elliott PM. Evolving story of clinical trials in hypertrophic cardiomyopathy. Circ Heart Fail 2018;11:e004572.
Murray GL, Colombo J. Ranolazine preserves and improves left ventricular ejection fraction and autonomic measures when added to guideline-driven therapy in chronic heart failure. Heart Int 2014;9:66–73.
Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J 2020;41:407-7.
Marciniak TA, Serebruany V. Ranolazine, ACE inhibitors, and angiotensin receptor blockers. Am J Med 2019;132:e844-5.
Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016;37:2129-2200.
Rambarat CA, Elgendy IY, Handberg EM, et al. Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction ancillary study. Int J Cardiol 2019;276:8-13.
Kosiborod M, Arnold SV, Spertus JA, et al. Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina. Results from the TERISA randomized clinical trial. J Am Coll Cardiol 2013;61:2038-45.
Jiménez-Corona AE, Damián-Zamacona S, Pérez-Torres A, et al. Osteopontin upregulation in atherogenesis is associated with cellular oxidative stress triggered by the activation of scavenger receptors. Arch Med Res 2012;43:102-11.
Terruzzi I, Montesano A, Senesi P, et al. Ranolazine promotes muscle differentiation and reduces oxidative stress in C2C12 skeletal muscle cells. Endocrine 2017;58:33-45.
Dhalla AK, Yang M, Ning Y, et al. Blockade of Na+ channels in pancreatic α-cells has antidiabetic effects. Diabetes 2014;63:3545-56.
Rizzetto R, Rocchetti M, Sala L, et al. Late sodium current (INaL) in pancreatic β-cells. Pflugers Arch 2015;467:1757-68.
Teoh IH, Banerjee M. Effect of ranolazine on glycaemia in adults with and without diabetes: a metaanalysis of randomised controlled trials. Open Heart 2018;5:e000706.
Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2020;41:255-323.
Iqbal Z, Azmi S, Yadav R, et al. Diabetic peripheral neuropathy: epidemiology, diagnosis, and pharmacotherapy. Clin Ther 2018;40:828–49.
Vikram A, Tripathi DN, Kumar A, Singh S. Oxidative stress and inflammation in diabetic complications. Int J Endocrinol 2014;2014:679754.
Feldman EL, Nave K-A, Jensen TS, Bennett DLH. New horizons in diabetic neuropathy: mechanisms, bioenergetics, and pain. Neuron 2017;93:1296-313.
Aldasoro M, Guerra-Ojeda S, Aguirre-Rueda D, et al. Valles, Effects of ranolazine on astrocytes and neurons in primary culture. PLoS One 2016;11:e0150619.
Gould H, Garrett C, Donahue RR, et al. Ranolazine attenuates behavioral signs of neuropathic pain. Behav Pharmacol 2009;20:755-8.
Ding S, Shen Z, Chen Y, et al. Pioglitazone can ameliorate insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats. Acta Pharmacol Sin 2005;26:575-80.
Griggs RB, Donahue RR, Adkins BG, et al. Pioglitazone inhibits the development of hyperalgesia and sensitization of spinal nociresponsive neurons in type 2 diabetes. J Pain 2016;17:359-73.
Yonutas HM, Sullivan PG, Targeting PPAR isoforms following CNS injury. Curr Drug Targets 2013;14:733-42.
Elkholy SE, Elaidy SM, El-Sherbeeny NA, et al. Neuroprotective effects of ranolazine versus pioglitazone in experimental diabetic neuropathy: Targeting Nav1.7 channels and PPAR-γ. Life Sci 2020;250:117557.
Geijselaers SLC, Sep SJS, Stehouwer CDA, Biessels GJ. Glucose regulation, cognition, and brain MRI in type 2 diabetes: A systematic review. Lancet Diabetes Endocrinol 2015;3:75-89.
Cassano V, Leo A, Tallarico M, et al. Metabolic and cognitive effects of ranolazine in type 2 diabetes mellitus: Data from an in vivo model. Nutrients 2020;12:382.
Ma A, Garland WT, Smith WB, et al. A pilot study of ranolazine in patients with intermittent claudication. Int Angiol 2006;25:361-9.
ClinicalTrials.gov [Internet]. Bethesda: National Library of Medicine. Supervised treadmill exercise and ranolazine for intermittent claudication of lower extremities (STERILE). 2009 Jun 4 - Identifier NCT00914316. Available from: https://www.clinicaltrials.gov/ct2/show/NCT00914316
Aboyans V, Ricco JB, Bartelink MEL, et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS). Eur Heart J 2018;39:763-816.
Frank U, Nikol S, Belch J, et al. ESVM Guideline on peripheral arterial disease. Vasa 2019;48:1-79.
Tuder RM, Archer SL, Dorfmüller P, et al. Relevant issues in the pathology and pathobiology of pulmonary hypertension. J Am Coll Cardiol 2013;62:d4–D12.
Galie N, Humbert M, Vachiery JL, et al. 2015 ESC/ ERS guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J 2015;46:903-75.
van de Veerdonk MC, Kind T, Marcus JT, et al. Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy. J Am Coll Cardiol 2011;58:2511-9.
Han Y, Forfia P, Vaidya A, et al. Ranolazine improves right ventricular function in patients with precapillary pulmonary hypertension: results from a double blinded randomized placebo-controlled trial. J Cardiac Fail 2021;27:253-7.
Khan SS, Cuttica MJ, Beussink-Nelson L, et al. Effects of ranolazine on exercise capacity, right ventricular indices, and hemodynamic characteristics in pulmonary arterial hypertension: a pilot study. Pulm Circ 2015;5:547-56.
Rosa GM, Dorighi U, Ferrero S, et al. Ranolazine for the treatment of atrial fibrillation. Expert Opin Investig Drugs 2015;24:825-36.
Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J 2021;42:373-498.
De Ferrari GM, Maier LS, Mont L, et al. Ranolazine in the treatment of atrial fibrillation: results of the dose-ranging RAFFAELLO (Ranolazine in Atrial Fibrillation Following an ELectricaL CardiOversion) study. Heart Rhythm 2015;12:872-8.
Reiffel JA, Camm AJ, Belardinelli L, et al. The HARMONY trial: combined ranolazine and dronedarone in the management of paroxysmal atrial fibrillation: mechanistic and therapeutic synergism. Circ Arhythm Electrophysiol 2015;8:1048-56.
Koskinas KC, Fragakis N, Katritsis D, et al. Ranolazine enhances the efficacy of amiodarone for conversion of recent-onset atrial fibrillation. Europace 2014;16:973-979.
De Vecchis R, Ariano C, Giasi A, Cioppa C. Antiarrhythmic effects of ranolazine used both alone for prevention of atrial fibrillation and as an add-on to intravenous amiodarone for its pharmacological cardioversion: a meta-analysis. Minerva Cardioangiol 2018;66:349-59.
Wolfes J, Ellermann C, Broer N, et al. Antiarrhythmic effect of ranolazine in combination with selective NCX-inhibition in an experimental model of atrial fibrillation. Pharmaceuticals (Basel) 2020;13:321.
Gupta T, Khera S, Kolte D, et al. Antiarrhythmic properties of ranolazine: a review of the current evidence. Int J Cardiol 2015;187:66-74.
Parikh A, Mantravadi R, Kozhevnikov D, et al. Ranolazine stabilizes cardiac ryanodine receptors: a novel mechanism for the suppression of early afterdepolarization and torsades de pointes in long QT type 2. Heart Rhythm 2012;9:953-60.
Chorin E, Hu D, Antzelevitch C, et al. Ranolazine for congenital long-QT syndrome type III: experimental and long-term clinical data. Circ Arrhythm Electrophysiol 2016;9:e004370.
Morita N, Lee JH, Xie Y, et al. Suppression of re-entrant and multifocal ventricular fibrillation by the late sodium current blocker ranolazine. J Am Coll Cardiol 2011;57:366–75.
Verrier RL, Pagotto VP, Kanas AF, et al. Low doses of ranolazine and dronedarone in combination exert potent protection against atrial fibrillation and vulnerability to ventricular arrhythmias during acute myocardial ischemia. Heart Rhythm 2013;10:121–7.
Frommeyer G, Schmidt M, Clauss C, et al. Further insights into the underlying electrophysiological mechanisms for reduction of atrial fibrillation by ranolazine in an experimental model of chronic heart failure. Eur J Heart Fail 2012;14:1322-31.
Chorro FJ, del Canto I, Brines L, et al. Ranolazine attenuates the electrophysiological effects of myocardial stretch in Langendorff-perfused rabbit hearts. Cardiovasc Drugs Ther 2015;29:231–41.
Moschovidis V, Simopoulos V, Stravela S, et al. Dose-dependent effects of ranolazine on reentrant ventricular arrhythmias induced after subacute myocardial infarction in rabbits. J Cardiovasc Pharmacol Ther 2020;25:65-71.
Cannon SC. Channelopathies of skeletal muscle excitability. Compr Physiol 2015;5:761-90.
Arnold WD, Kline D, Sanderson A, et al. Open-label trial of ranolazine for the treatment of myotonia congenita. Neurology 2017;89:710-3.
Lorusso S, Kline D, Bartlett A, et al. Open-label trial of ranolazine for the treatment of paramyotonia congenita. Muscle Nerve 2019;59:240-3.
Stunnenberg BC, LoRusso S, Arnold WD, et al. Guidelines on clinical presentation and management of nondystrophic myotonias. Muscle Nerve 2020;62:430-44.
How to Cite
Uran, Carlo. 2021. “Through the Heart and Beyond: A Review on Ranolazine”. Monaldi Archives for Chest Disease 92 (1). https://doi.org/10.4081/monaldi.2021.1806.
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