Ranolazine: A review of its use in chronic stable angina pectoris

Drugs

Volumn 68, Issue 17, 2008, Pages 2483-2503

  Keating, Gillian M ^a,b  

^a ADIS INTERNATIONAL LIMITED   (New Zealand)

^b WOLTERS KLUWER HEALTH   (United States)

Author keywords

Adis Drug Evaluations; Angina pectoris; Controlled release drugs; Ranolazine, general

Indexed keywords

AMLODIPINE; ATENOLOL; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; CARBAMAZEPINE; CIMETIDINE; DIGOXIN; DILTIAZEM; GLYCERYL TRINITRATE; HYPERICUM PERFORATUM EXTRACT; PAROXETINE; PHENOBARBITAL; PHENYTOIN; PLACEBO; RANOLAZINE; RIFAMPICIN; SIMVASTATIN; VERAPAMIL;

ACUTE CORONARY SYNDROME; ADD ON THERAPY; ANGINA PECTORIS; ASTHENIA; BRADYCARDIA; CARDIOVASCULAR EFFECT; CLINICAL TRIAL; CONSTIPATION; COUGHING; DIABETES MELLITUS; DIZZINESS; DRUG ABSORPTION; DRUG ACTIVITY; DRUG CONTRAINDICATION; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DRUG TOLERABILITY; DRUG WITHDRAWAL; EOSINOPHIL COUNT; FATIGUE; GLYCEMIC CONTROL; HEADACHE; HEART ATRIUM FIBRILLATION; HEART MUSCLE ISCHEMIA; HEART VENTRICLE FUNCTION; HEMODYNAMICS; HUMAN; HYPERTENSION; MONOTHERAPY; NAUSEA; PERIPHERAL EDEMA; PHARMACODYNAMICS; QT INTERVAL; REVIEW; SIDE EFFECT; SUPRAVENTRICULAR TACHYCARDIA; SYNCOPE; TORSADE DES POINTES; UNCONSCIOUSNESS;

ACETANILIDES; ANGINA PECTORIS; CARDIOVASCULAR AGENTS; CHRONIC DISEASE; DELAYED-ACTION PREPARATIONS; HUMANS; PIPERAZINES;

ANGINA;

EID: 56749180947     PISSN: 00126667     EISSN: 00126667     Source Type: Journal    
DOI: 10.2165/0003495-200868170-00006     Document Type: Review

References (74)

1. Allender S, Scarborough P, Peto V, et al. European cardiovascular disease statistics: 2008 edition [online]. Available from URL: http://www.ehnheart.org/ files/statistics%202008%20web-161229A.pdf [Accessed 2008 Aug 12]
2. Fox K, Garcia MA, Ardissino D, et al. Guidelines on the management of stable angina pectoris: executive summary: the task force on the management of stable angina pectoris of the European Society of Cardiology. Eur Heart J 2006 Jun; 27 (11): 1341-81
3. Scirica BM, Morrow DA. Ranolazine in patients with angina and coronary artery disease. Curr Cardiol Rep 2007 Jul; 9 (4): 272-8
4. European Medicines Agency. Ranexa (ranolazine): EU summary of product characteristics [online]. Available from URL: http://www.emea.europa.eu [Accessed 2008 Aug 5]
5. Dobesh PP, Trujillo TC. Ranolazine: a new option in the management of chronic stable angina. Pharmacotherapy 2007 Dec; 27 (12): 1659-76
6. Jerling M. Clinical pharmacokinetics of ranolazine. Clin Pharmacokinet 2006; 45 (5): 469-91
7. Bassand J-P. Clinical implications of inhibition of the late sodium current: ranolazine. Eur Heart J Suppls 2006; 8 Suppl. A: A14-9
8. Saint DA. The cardiac persistent sodium current: an appealing therapeutic target? Br J Pharmacol 2008 Mar; 153 (6): 1133-42
9. Shryock JC, Belardinelli L. Inhibition of late sodium current to reduce electrical and mechanical dysfunction of ischaemic myocardium. Br J Pharmacol 2008 Mar; 153 (6): 1128-32
10. Hale SL, Shryock JC, Belardinelli L, et al. Late sodium current inhibition as a new cardioprotective approach. J Mol Cell Cardiol 2008 Jun; 44 (6): 954-67
11. 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 May; 148 (1): 16-24
12. Antzelevitch C, Belardinelli L, Zygmunt AC, et al. Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation 2004 Aug 24; 110 (8): 904-10
13. 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 May; 17 Suppl. 1: S169-77
14. Sossalla S, Wagner S, Rasenack ECL, 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 Jul; 45 (1): 32-43
15. 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
16. Na in guinea pig ventricular myocytes. J Cardiovascul Pharmacol 2004 Aug; 44 (2): 192-9
17. 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
18. 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
19. 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. Epub 2008 Jul 25
20. 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 Dec; 41 (6): 1031-8
21. 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 Feb; 28 (2): 341-50
22. McCormack JG, Barr RL, Wolff AA, et al. Ranolazine stimulates glucose oxidation in normoxic, ischemic, and reperfused ischemic rat hearts. Circulation 1996 Jan 1; 93 (1): 135-42
23. MacInnes A, Fairman DA, Binding P, et al. The antianginal agent trimetazidine does not exert its functional benefit via inhibition of mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res 2003 Aug 8; 93 (3): e26-32
24. Wang P, Fraser H, Lloyd SG, et al. A comparison between ranolazine and CVT-4325, a novel inhibitor of fatty acid oxidation, on cardiac metabolism and left ventricular function in rat isolated perfused heart during ischemia and reperfusion. J Pharmacol Exp Ther 2007 Apr; 321 (1): 213-20
25. 2-adrenoceptor antagonist in the rat cardiovascular system. Naunyn Schmiedebergs Arch Pharmacol 2001 Apr; 363 (4): 464-71
26. Bagger JP, Bøtker HE, Thomassen A, et al. Effects of ranolazine on ischemic threshold, coronary sinus blood flow, and myocardial metabolism in coronary artery disease. Cardiovasc Drugs Ther 1997 Jul; 11 (3): 479-84
27. 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 Apr 21; 43 (8): 1375-82
28. 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 Jan 21; 291 (3): 309-16
29. Cocco G, Rousseau MF, Bouvy T, et al. Effects of a new metabolic modulator, ranolazine, on exercise tolerance in angina pectoris patients treated with β-blocker or diltiazem. J Cardiovasc Pharmacol 1992 Jul; 20 (1): 131-8
30. Jain D, Dasgupta P, Hughes LO, et al. Ranolazine (RS-43285): a preliminary study of a new anti-anginal agent with selective effect on ischaemic myocardium. Eur J Clin Pharmacol 1990; 38 (2): 111-4
31. Pepine CJ, Wolff AA. A controlled trial with a novel anti-ischemic agent, ranolazine, in chronic stable angina pectoris that is responsive to conventional antianginal agents. Ranolazine Study Group. Am J Cardiol 1999 Jul 1; 84 (1): 46-50
32. Rousseau MF, Pouleur H, Cocco G, et al. Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris. Am J Cardiol 2005 Feb 1; 95 (3): 311-6
33. 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 Aug 1; 48 (3): 566-75
34. Thadani U, Ezekowitz M, Fenney L, et al. Double-blind efficacy and safety study of a novel anti-ischemic agent, ranolazine, versus placebo in patients with chronic stable angina pectoris. Circulation 1994 Aug; 90 (2): 726-34
35. 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 Oct; 8 (5): 741-7
36. Stone PH, Chaitman B, Koren A, et al. Effects of ranolazine as monotherapy and combination therapy on rate pressure product at rest and during exercise: results from the MARISA and CARISA trials [abstract no. 3362]. Circulation 2006 Oct 31; 114 (18 Suppl.): 715
37. Rajamani S, Shryock JC, Belardinelli L. Rapid kinetic interactions of ranolazine with HERG K+ current. J Cardiovasc Pharmacol 2008 Jun; 51 (6): 581-9
38. 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 Oct; 19 (10): 1073-9
39. Burashnikov A, Di Diego JM, Zygmunt AC, et al. Atrium-selective sodium channel block as a strategy for suppression of atrial fibrillation: differences in sodium channel inactivation between atria and ventricles and the role of ranolazine. Circulation 2007 Sep 25; 116 (13): 1449-57
40. 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
41. 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 Jun; 325 (3): 875-81
42. 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 Apr; 1 (2): 141-8
43. 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 May; 77 (1): 31-9
44. Gralinski MR, Black SC, Kilgore KS, et al. Cardioprotective effects of ranolazine (RS-43285) in the isolated perfused rabbit heart. Cardiovasc Res 1994 Aug; 28 (8): 1231-7
45. 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 Aug 23; 91 (4): 278-80
46. 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 Dec; 8 (6): 416-22
47. 1c in patients with chronic angina and diabetes. Eur Heart J 2006; 27 (1): 42-8
48. Morrow DA, Scirica BM, Chaitman BR, et al. Effect of ranolazine on hemoglobin A1c in the MERLIN-TIMI 36 randomized controlled trial [abstract no. 2453]. Circulation 2007 Oct 16; 116 (16 Suppl. II): 539-40
49. 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 Apr 25; 297 (16): 1775-83
50. CV Therapeutics, Inc. Ranexa® (ranolazine extended-release tablets): US prescribing information [online]. Available from URL: http://www.cvt.com/pdf/ Ranexa%20PI%20L000025%201108.pdf [Accessed 2008 Jul 23]
51. 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
52. Chu N, Sohoo D, Sun H-L, et al. In vitro metabolism of ranolazine [abstract no. 363]. Drug Metab Rev 2003; 35 Suppl. 2: 182
53. 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 Apr; 45 (4): 422-33
54. 14C]- ranolazine in humans [abstract no. 98]. Drug Metab Rev 2003; 35 Suppl. 2: 49
55. Abdallah H, Jerling M. Effect of hepatic impairment on the multiple-dose pharmacokinetics of ranolazine sustained-release tablets. J Clin Pharmacol 2005 Jul; 45 (7): 802-9
56. Jerling M, Abdallah H. Effect of renal impairment on multiple-dose pharmacokinetics of extended-release ranolazine. Clin Pharmacol Ther 2005 Sep; 78 (3): 288-97
57. Parker J, Chaitman B, Skopal J, et al. Rebound worsening in exercise performance was not observed after abrupt ranolazine withdrawal in patients with chronic angina in CARISA [abstract no. 188]. Eur Heart J 2003; 24 Suppl. 1: 20
58. 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
59. 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 Jan 1; 99 (1): 11-8
60. 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 Nov 5; 106 (19 Suppl. II): 349-50
61. European Medicines Agency. CHMP assessement report for Ranexa (ranolazine) [online]. Available from URL: http://www.emea.europa.eu [Accessed 2008 Aug 5]
62. Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, et al. Evaluation of a novel anti-ischemic agent in acute coronary syndromes: design and rationale for the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation acute coronary syndromes (MERLIN)-TIMI 36 trial. Am Heart J 2006 Aug; 152 (2): 400e.1-9
63. Arnold SV, Morrow DA, Wang K, et al. Effects of ranolazine on disease-specific health status and quality of life: results from the MERLIN-TIMI 36 randomized trial [abstract no. 1024-54]. J Am Coll Cardiol 2008 Mar 11; 51 (10 Suppl. A): A215
64. Mega JL, Hochman JS, Scirica BM, et al. Anti-ischemic effects of ranolazine in women: results from the randomized, placebo-controlled MERLIN-TIMI 36 trial [abstract no. 2451]. Circulation 2007 Oct 16; 116 (16 Suppl. II): 539
65. Wilson SR, Morrow DA, Scirica BM, et al. Efficacy and safety of ranolazine in chronic angina: observations from the randomized, double-blind, placebo-controlled MERLIN-TIMI 36 Trial [abstract no. 1031-45]. J Am Coll Cardiol 2008 Mar 11; 51 (10 Suppl. A): A225
66. 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 Mar 13; 49 (10): 1027-34
67. 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 Oct 9; 116 (15): 1647-52
68. Gibbons RJ, Abrams J, Chatterjee K, et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (committee to update the 1999 guidelines for the management of patients with chronic stable angina) [online]. Available from URL: http://www.acc.org/clinical/guidelines/stable/stable.pdf [Accessed 2008 Aug 5]
69. 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 Apr 12; 356 (15): 1503-16
70. Melloni C, Newby LK. Metabolic efficiency with ranolazine for less ischemia in non-ST elevation acute coronary syndromes (MERLIN TIMI-36) study. Expert Rev Cardiovasc Ther 2008 Jan; 6 (1): 9-16
71. Newby LK, Peterson ED. Does ranolazine have a place in the treatment of acute coronary syndromes? JAMA 2007 Apr 25; 297 (16): 1823-5
72. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (writing committee to revise the 2002 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction). Circulation 2007 Aug 14; 116 (7): e148-304
73. Chaitman BR. Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation 2006 May 23; 113 (20): 2462-72
74. Cobbe S. Electrophysiological perspectives: what has ranolazine taught us? Eur Heart J Suppls 2004; 6 Suppl. 1: I9-I11