Ranolazine: A review of its use as add-on therapy in patients with chronic stable angina pectoris

Drugs

Volumn 73, Issue 1, 2013, Pages 55-73

  Keating, Gillian M ^a  

^a Adis 41 ^*  (New Zealand)

Author keywords

[No Author keywords available]

Indexed keywords

AMIODARONE; AMLODIPINE; ATENOLOL; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; CARBAMAZEPINE; CLARITHROMYCIN; CYCLOSPORIN A; DIGOXIN; DILTIAZEM; ERYTHROMYCIN; FLUCONAZOLE; GLYCERYL TRINITRATE; ITRACONAZOLE; IVABRADINE; KETOCONAZOLE; NEFAZODONE; NICORANDIL; NITRATE; PHENOBARBITAL; PHENYTOIN; PLACEBO; POSACONAZOLE; PROTEINASE INHIBITOR; RANOLAZINE; RIFAMPICIN; SIMVASTATIN; TELITHROMYCIN; UNINDEXED DRUG; VORICONAZOLE;

ADD ON THERAPY; ANTIARRHYTHMIC ACTIVITY; AREA UNDER THE CURVE; ASTHENIA; CARDIAC PATIENT; CARDIOVASCULAR MORTALITY; CLINICAL TRIAL (TOPIC); CONGESTIVE HEART FAILURE; CONSTIPATION; CORONARY ARTERY DISEASE; DIZZINESS; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG DOSE INCREASE; DRUG DOSE TITRATION; DRUG EFFECT; DRUG EFFICACY; DRUG EXCRETION; DRUG INDUCED HEADACHE; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; ELECTROCARDIOGRAM; EXERCISE TOLERANCE; FAINTNESS; HEART FUNCTION; HEART HEMODYNAMICS; HIGH RISK POPULATION; HUMAN; IC 50; MAXIMUM PLASMA CONCENTRATION; NAUSEA; NON ST SEGMENT ELEVATION ACUTE CORONARY SYNDROME; NON ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; NONHUMAN; OFF LABEL DRUG USE; PERIPHERAL EDEMA; PLASMA CONCENTRATION-TIME CURVE; QT INTERVAL; REVIEW; STABLE ANGINA PECTORIS; SYSTEMATIC REVIEW;

ACETANILIDES; ANGINA, STABLE; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; HUMANS; PIPERAZINES; TREATMENT OUTCOME;

ANGINA;

EID: 84877071214     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: 10.1007/s40265-012-0005-z     Document Type: Review

References (88)

1. Lopez-Sendon J, Purcell H, Camici P, et al. Chronic stable angina guidelines: is there an emerging international consensus? Br J Cardiol. 2012;19(Suppl. 2):S2-11.
2. Boden WE, O'Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007;356(15):1503-16.
3. Chaitman BR, Skettino SL, Parker JO, et al. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol. 2004;43(8):1375-82.
4. European Medicines Agency. Ranexa (ranolazine): EU summary of product characteristics. 2011. http://www.ema.europa.eu/ema/index.jsp?curl=pages/ medicines/human/medicines/000805/human-med-001009.jsp&mid= WC0b01ac058001d124. Accessed 12 Sep 2012.
5. Keating GM. Ranolazine: a review of its use in chronic stable angina pectoris. Drugs. 2008;68(17):2483-503.
6. Jerling M. Clinical pharmacokinetics of ranolazine. Clin Pharmacokinet. 2006;45(5):469-91.
7. Hasenfuss G, Maier LS. Mechanism of action of the new anti-ischemia drug ranolazine. Clin Res Cardiol. 2008;97(4):222-6.
8. Belardinelli L, Shryock JC, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine. Heart. 2006;92(Suppl. 4):iv6-iv14.
9. Na using ranolazine. J Cardiovasc Pharmacol. 2009;54(4):279-86.
10. Sossalla S, Maier LS. Role of ranolazine in angina, heart failure, arrhythmias, and diabetes. Pharmacol Ther. 2012;133(3):311-23.
11. Antzelevitch C, Belardinelli L, Zygmunt AC, et al. Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation. 2004;110(8):904-10.
12. Undrovinas AI, Belardinelli L, Undrovinas NA, et al. Ranolazine improves abnormal repolarization and contraction in left ventricular myocytes of dogs with heart failure by inhibiting late sodium current. J Cardiovasc Electrophysiol. 2006;17(Suppl. 1):S169-77.
13. Na in guinea pig ventricular myocytes. J Cardiovasc Pharmacol. 2004;44(2):192-9.
14. Song Y, Shryock JC, Wagner S, et al. Blocking late sodium current reduces hydrogen peroxide-induced arrhythmogenic activity and contractile dysfunction. J Pharmacol Exp Ther. 2006;318(1):214-22.
15. Sossalla S, Wagner S, Rasenack EC, et al. Ranolazine improves diastolic dysfunction in isolated myocardium from failing human hearts: role of late sodium current and intracellular ion accumulation. J Mol Cell Cardiol. 2008;45(1):32-43.
16. Fredj S, Sampson KJ, Liu H, et al. Molecular basis of ranolazine block of LQT-3 mutant sodium channels: evidence for site of action. Br J Pharmacol. 2006;148(1):16-24.
17. Zhang XQ, Yamada S, Barry WH. Ranolazine inhibits an oxidative stress-induced increase in myocyte sodium and calcium loading during simulated-demand ischemia. J Cardiovasc Pharmacol. 2008;51(5):443-9.
18. Fraser H, Belardinelli L, Wang L, et al. Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol. 2006;41(6):1031-8.
19. Venkataraman R, Belardinelli L, Blackburn B, et al. A study of the effects of ranolazine using automated quantitative analysis of serial myocardial perfusion images. JACC Cardiovasc Imaging. 2009;2(11):1301-9.
20. Chaitman BR, Pepine CJ, Parker JO, et al. Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA. 2004;291(3):309-16.
21. Zhao G, Walsh E, Shryock JC, et al. Antiadrenergic and hemodynamic effects of ranolazine in conscious dogs. J Cardiovasc Pharmacol. 2011;57(6):639-47.
22. Stone PH, Chaitman BR, Stocke K, et al. The anti-ischemic mechanism of action of ranolazine in stable ischemic heart disease. J Am Coll Cardiol. 2010;56(12):934-42.
23. Stone PH, Gratsiansky NA, Blokhin A, et al. Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol. 2006;48(3):566-75.
24. Venkataraman R, Aljaroudi W, Belardinelli L, et al. The effect of ranolazine on the vasodilator-induced myocardial perfusion abnormality. J Nucl Cardiol. 2011;18(3):456-62.
25. Wu L, Shryock JC, Song Y, et al. An increase in late sodium current potentiates the proarrhythmic activities of low-risk QT-prolonging drugs in female rabbit hearts. J Pharmacol Exp Ther. 2006;316(2):718-26.
26. Wu L, Shryock JC, Song Y, et al. Antiarrhythmic effects of ranolazine in a guinea pig in vitro model of long-QT syndrome. J Pharmacol Exp Ther. 2004;310(2):599-605.
27. Wang W-Q, Robertson C, Dhalla AK, et al. Antitorsadogenic effects of (±)-N-(2,6-dimethyl-phenyl)-(4[2-hydroxy-3-(2-methoxyphenoxy)propyl] -1-piperazine (ranolazine) in anesthetized rabbits. J Pharmacol Exp Ther. 2008;325(3):875-81.
28. Schram G, Zhang L, Derakhchan K, et al. Ranolazine: ion-channel-blocking actions and in vivo electrophysiological effects. Br J Pharmacol. 2004;142(8):1300-8.
29. Gralinski MR, Chi L, Park JL, et al. Protective effects of ranolazine on ventricular fibrillation induced by activation of the ATP-dependent potassium channel in the rabbit heart. J Cardiovasc Pharmacol Ther. 1996;1(2):141-8.
30. Kloner RA, Dow JS, Bhandari A. The antianginal agent ranolazine is a potent antiarrhythmic agent that reduces ventricular arrhythmias: through a mechanism favoring inhibition of late sodium channel. Cardiovasc Ther. 2011;29(4):e36-41.
31. Sicouri S, Glass A, Belardinelli L, et al. Antiarrhythmic effects of ranolazine in canine pulmonary vein sleeve preparations. Heart Rhythm. 2008;5(7):1019-26.
32. Dhalla AK, Wang W-Q, Dow J, et al. Ranolazine, an antianginal agent, markedly reduces ventricular arrhythmias induced by ischemia and ischemia-reperfusion. Am J Physiol Heart Circ Physiol. 2009;297(5):H1923-9.
33. Kumar K, Nearing BD, Bartoli CR, et al. Effect of ranolazine on ventricular vulnerability and defibrillation threshold in the intact porcine heart. J Cardiovasc Electrophysiol. 2008;19(10):1073-9.
34. 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(3):366-75.
35. Matsumura H, Hara A, Hashizume H, et al. Protective effects of ranolazine, a novel anti-ischemic drug, on the hydrogen peroxide-induced derangements in isolated, perfused rat heart: comparison with dichloroacetate. Jpn J Pharmacol. 1998;77(1):31-9.
36. Hwang H, Arcidi JM Jr, Hale SL, et al. Ranolazine as a cardioplegia additive improves recovery of diastolic function in isolated rat hearts. Circulation. 2009;120(Suppl. 1):S16-21.
37. Hwang H, Arcidi JM Jr, Hale SL, et al. Ranolazine as an adjunct to cardioplegia: a potential new therapeutic application. J Cardiovasc Pharmacol Ther. 2009;14(2):125-33.
38. Rastogi S, Sharov VG, Mishra S, et al. Ranolazine combined with enalapril or metoprolol prevents progressive LV dysfunction and remodeling in dogs with moderate heart failure. Am J Physiol Heart Circ Physiol. 2008;295(5):H2149-55.
39. Gralinski MR, Black SC, Kilgore KS, et al. Cardioprotective effects of ranolazine (RS-43285) in the isolated perfused rabbit heart. Cardiovasc Res. 1994;28(8):1231-7.
40. Sabbah HN, Chandler MP, Mishima T, et al. Ranolazine, a partial fatty acid oxidation (pFOX) inhibitor, improves left ventricular function in dogs with chronic heart failure. J Card Fail. 2002;8(6):416-22.
41. Chandler MP, Stanley WC, Morita H, et al. Short-term treatment with ranolazine improves mechanical efficiency in dogs with chronic heart failure. Circ Res. 2002;91(4):278-80.
42. Hayashida W, van Eyll C, Rousseau MF, et al. Effects of ranolazine on left ventricular regional diastolic function in patients with ischemic heart disease. Cardiovasc Drugs Ther. 1994;8(5):741-7.
43. Moss AJ, Zareba W, Schwarz KQ, et al. Ranolazine shortens repolarization in patients with sustained inward sodium current due to type-3 long-QT syndrome. J Cardiovasc Electrophysiol. 2008;19(12):1289-93.
44. Maier L, Wachter R, Edelmann F, et al. Ranolazine for the treatment of diastolic heart failure in patients with preserved ejection fraction: results from the RALI-DHF study (abstract no. 921-8). 61st Annual Scientific Sessions of the American College of Cardiology, Chicago 24-27 Mar 2012.
45. Jacobshagen C, Belardinelli L, Hasenfuss G, et al. Ranolazine for the treatment of heart failure with preserved ejection fraction: background, aims, and design of the RALI-DHF study. Clin Cardiol. 2011;34(7):426-32.
46. Figueredo VM, Pressman GS, Romero-Corral A, et al. Improvement in left ventricular systolic and diastolic performance during ranolazine treatment in patients with stable angina. J Cardiovasc Pharmacol Ther. 2011;16(2):168-72.
47. Venkataraman R, Chen J, Garcia EV, et al. Effect of ranolazine on left ventricular dyssynchrony in patients with coronary artery disease. Am J Cardiol. 2012;110(10):1440-5.
48. 1c in patients with chronic angina and diabetes. Eur Heart J. 2006;27(1):42-8.
49. Morrow DA, Scirica BM, Chaitman BR, et al. Evaluation of the glycometabolic effects of ranolazine in patients with and without diabetes mellitus in the MERLIN-TIMI 36 randomized controlled trial. Circulation. 2009;119(15):2032-9.
50. Chisholm JW, Goldfine AB, Dhalla AK, et al. Effect of ranolazine on A1C and glucose levels in hyperglycemic patients with non-ST elevation acute coronary syndrome. Diabetes Care. 2010;33(6):1163-8.
51. Ning Y, Zhen W, Fu Z, et al. Ranolazine increases β-cell survival and improves glucose homeostasis in low-dose streptozotocin-induced diabetes in mice. J Pharmacol Exp Ther. 2011;337(1):50-8.
52. Deshmukh SH, Patel SR, Pinassi E, et al. Ranolazine improves endothelial function in patients with stable coronary artery disease. Coron Artery Dis. 2009;20(5):343-7.
53. Penman AD, Eadie J, Herron WJ, et al. The characterization of the metabolites of ranolazine in man by liquid chromatography mass spectrometry. Rapid Commun Mass Spectrom. 1995;9(14):1418-30.
54. Jerling M, Abdallah H. Effect of renal impairment on multiple-dose pharmacokinetics of extended-release ranolazine. Clin Pharmacol Ther. 2005;78(3):288-97.
55. Abdallah H, Jerling M. Effect of hepatic impairment on the multiple-dose pharmacokinetics of ranolazine sustained-release tablets. J Clin Pharmacol. 2005;45(7):802-9.
56. Jerling M, Huan B-L, Leung K, et al. Studies to investigate the pharmacokinetic interactions between ranolazine and ketoconazole, diltiazem, or simvastatin during combined administration in healthy subjects. J Clin Pharmacol. 2005;45(4):422-33.
57. Wang X, Bingham J, DeVault A, et al. Pharmacokinetic interaction between ranolazine and the CYP2D6 substrate metoprolol in healthy volunteers (abstract no. 72). J Clin Pharmacol. 2009;49(9):1107.
58. 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(16):1775-83.
59. Bennett NM, Arndt TL, Iyer V, et al. Ranolazine refractory angina registry trial: 1-year results (abstract no. 1074-362). J Am Coll Cardiol. 2011;57(14):E1050.
60. López-Sendón J, Lee S, Cheng ML, et al. Effects of ranolazine on exercise tolerance and angina frequency in patients with severe chronic angina receiving maximally-tolerated background therapy: analysis from the Combination Assessment of Ranolazine In Stable Angina (CARISA) randomized trial. Eur J Prev Cardiol. 2012;19(5):952-9.
61. White HD, Skettino S, Chaitman BR, et al. Anti-anginal efficacy of ranolazine addition to beta blocker or calcium antagonist therapy in patients with a history of heart failure (abstract no. 1746). Circulation. 2002;106 (19 Suppl. 2):349-50.
62. Wenger NK, Chaitman B, Vetrovec GW. Gender comparison of efficacy and safety of ranolazine for chronic angina pectoris in four randomized clinical trials. Am J Cardiol. 2007;99(1):11-8.
63. Rich MW, Crager M, McKay CR. Safety and efficacy of extended-release ranolazine in patients aged 70 years or older with chronic stable angina pectoris. Am J Geriatr Cardiol. 2007;16(4):216-21.
64. Arnold SV, Morrow DA, Wang K, et al. Effects of ranolazine on disease-specific health status and quality of life among patients with acute coronary syndromes: results from the MERLIN-TIMI 36 randomized trial. Circ Cardiovasc Qual Outcomes. 2008;1(2):107-15.
65. Wilson SR, Scirica BM, Braunwald E, et al. Efficacy of ranolazine in patients with chronic angina: observations from the randomized, double-blind, placebo-controlled MERLIN-TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Segment Elevation Acute Coronary Syndromes) 36 Trial. J Am Coll Cardiol. 2009;53(17):1510-6.
66. Mega JL, Hochman JS, Scirica BM, et al. Clinical features and outcomes of women with unstable ischemic heart disease: observations from metabolic efficiency with ranolazine for less ischemia in non-ST-elevation acute coronary syndromes-thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36). Circulation. 2010;121(16):1809-17.
67. Morrow DA, Scirica BM, Sabatine MS, et al. B-type natriuretic peptide and the effect of ranolazine in patients with non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary- Thrombolysis In Myocardial Infarction 36) trial. J Am Coll Cardiol. 2010;55(12):1189-96.
68. Scirica BM, Morrow DA, Budaj A, et al. Ischemia detected on continuous electrocardiography after acute coronary syndrome: observations from the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 36) trial. J Am Coll Cardiol. 2009;53(16):1411-21.
69. Koren MJ, Crager MR, Sweeney M. Long-term safety of a novel antianginal agent in patients with severe chronic stable angina: the Ranolazine Open Label Experience (ROLE). J Am Coll Cardiol. 2007;49(10):1027-34.
70. Scirica BM, Morrow DA, Hod H, et al. Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non-ST-segment-elevation acute coronary syndrome: results from the metabolic efficiency with ranolazine for less ischemia in non-ST-elevation acute coronary syndrome-thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation. 2007;116(15):1647-52.
71. Scirica BM, Braunwald E, Belardinelli L, et al. Relationship between nonsustained ventricular tachycardia after non-ST-elevation acute coronary syndrome and sudden cardiac death: observations from the metabolic efficiency with ranolazine for less ischemia in non-ST-elevation acute coronary syndrome-thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation. 2010;122(5):455-62.
72. Scirica BM, Belardinelli L, Chaitman BR, et al. Effect of ranolazine on atrial fibrillation among patients with non-ST elevation acute coronary syndromes (NSTEACS): observations from the MERLIN-TIMI 36 trial (abstract no. 13798). Circulation. 2011;124(21 suppl 1)
73. Boden WE. Ranolazine and its anti-ischemic effects: revisiting an old mechanistic paradigm anew? J Am Coll Cardiol. 2010;56(12):943-5.
74. National Institute for Health and Clinical Excellence. Management of stable angina. 2011. http://www.nice.org.uk/nicemedia/live/13549/55660/55660. pdf. Accessed 27 Sep 2012.
75. Deedwania PC, Carbajal EV. Medical therapy versus myocardial revascularization in chronic coronary syndrome and stable angina. Am J Med. 2011;124(8):681-8.
76. ®) in the treatment of chronic stable angina. Adv Ther. 2010;27(4):193-201.
77. Truffa AA, Newby LK, Melloni C. Extended-release ranolazine: critical evaluation of its use in stable angina. Vasc Health Risk Manag. 2011;7:535-9.
78. Zuchi C, Tritto I, Ambrosio G. Angina pectoris in women: focus on microvascular disease. Epub Int J Cardiol; 2012
79. Mehta PK, Goykhman P, Thomson LEJ, et al. Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. JACC Cardiovasc Imaging. 2011;4(5):514-22.
80. Belsey J, Vardas P, Camm J. Relative efficacy of antianginal drugs used in an add-on role in patients with stable angina: systematic review and meta-analysis (abstract no. 15298). Circulation. 2012;126(21 Suppl.).
81. European Medicines Agency. Corlentor (ivabradine): EU summary of product characteristics. 2012. http://www.emea.europa.eu/docs/en-GB/document-library/ EPAR-Product-Information/human/000598/WC500035341.pdf. Accessed 19 Nov 2012.
82. Cingolani E, Lepor NE, Singh BN. The electrophysiological properties of ranolazine: a metabolic anti-ischemic drug or an energy-efficient antiarrhythmic agent? Rev Cardiovasc Med. 2011;12(3):136-42.
83. Murdock DK, Reiffel JA, Kaliebe J, et al. The conversion of paroxysmal or initial onset atrial fibrillation with oral ranolazine: implications for a new 'pill-in-pocket' approach in structural heart disease. J Atr Fibrillation. 2010;2(1):705-10.
84. Murdock DK, Kaliebe J, Larrain G. The use of ranolazine to facilitate electrical cardioversion in cardioversion-resistant patients: a case series. Pacing Clin Electrophysiol. 2012;35(3):302-7.
85. Fragakis N, Koskinas KC, Katritsis DG, et al. Comparison of effectiveness of ranolazine plus amiodarone versus amiodarone alone for conversion of recent-onset atrial fibrillation. Am J Cardiol. 2012;110(5):673-7.
86. Menarini Group. Ranolazine in atrial fibrillation following an electricaL cardioversion (RAFFAELLO) [ClinicalTrials.gov identifier NCT01534962]. US National Institutes of Health, ClinicalTrials.gov (online). 2012. http://clinicaltrials.gov. Accessed 19 Nov 2012.
87. Gilead Sciences. A study to evaluate the effect of ranolazine and dronedarone when given alone and in combination in patients with paroxysmal atrial fibrillation (HARMONY) [ClinicalTrials.gov identifier NCT01522651]. US National Institutes of Health, ClinicalTrials.gov (online). 2012. http://clinicaltrials.gov. Accessed 19 Nov 2012.
88. Pelliccia F, Pasceri V, Marazzi G, et al. A pilot randomized study of ranolazine for reduction of myocardial damage during elective percutaneous coronary intervention. Am Heart J. 2012;163(6):1019-23.