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New therapies for angina pectoris

Authors
Michael Simons, MD
Roger J Laham, MD
Section Editor
Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
Deputy Editor
Gordon M Saperia, MD, FACC

INTRODUCTION

Despite the increasing success of conventional medical therapies and the continued development and improvement of percutaneous coronary intervention (PCI), a significant number of patients with ischemic heart disease and angina pectoris cannot be successfully managed.

Many of these patients are not candidates for revascularization by PCI or coronary artery bypass graft surgery (CABG) because of one or more of the following [1]:

Unsuitable anatomy, such as diffuse coronary disease.

One or several prior PCIs or CABGs, which may limit further benefit or preclude further revascularization.

Lack of vascular conduits for CABG.

                             

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Literature review current through: Nov 2016. | This topic last updated: Tue Jun 28 00:00:00 GMT+00:00 2016.
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References
Top
  1. Mannheimer C, Camici P, Chester MR, et al. The problem of chronic refractory angina; report from the ESC Joint Study Group on the Treatment of Refractory Angina. Eur Heart J 2002; 23:355.
  2. Kim MC, Kini A, Sharma SK. Refractory angina pectoris: mechanism and therapeutic options. J Am Coll Cardiol 2002; 39:923.
  3. Yang EH, Barsness GW, Gersh BJ, et al. Current and future treatment strategies for refractory angina. Mayo Clin Proc 2004; 79:1284.
  4. Chaitman BR. Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation 2006; 113:2462.
  5. Beyder A, Strege PR, Reyes S, et al. Ranolazine decreases mechanosensitivity of the voltage-gated sodium ion channel Na(v)1.5: a novel mechanism of drug action. Circulation 2012; 125:2698.
  6. Stone PH. Ranolazine: new paradigm for management of myocardial ischemia, myocardial dysfunction, and arrhythmias. Cardiol Clin 2008; 26:603.
  7. 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.
  8. 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; 291:309.
  9. 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; 48:566.
  10. 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; 43:1375.
  11. 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 (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina). J Am Coll Cardiol 2013; 61:2038.
  12. Weisz G, Généreux P, Iñiguez A, et al. Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 2016; 387:136.
  13. 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; 53:1510.
  14. 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; 119:2032.
  15. "The Pink Sheet". Ranexa angina approval limited due to cardiac safety issue. F-D-C Reports 2006; 68:3.
  16. Schram G, Zhang L, Derakhchan K, et al. Ranolazine: ion-channel-blocking actions and in vivo electrophysiological effects. Br J Pharmacol 2004; 142:1300.
  17. Antzelevitch C, Belardinelli L, Wu L, et al. Electrophysiologic properties and antiarrhythmic actions of a novel antianginal agent. J Cardiovasc Pharmacol Ther 2004; 9 Suppl 1:S65.
  18. 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; 49:1027.
  19. Singh BN, Wadhani N. Antiarrhythmic and proarrhythmic properties of QT-prolonging antianginal drugs. J Cardiovasc Pharmacol Ther 2004; 9 Suppl 1:S85.
  20. 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; 116:1647.
  21. Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2012; 126:e354.
  22. Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2012; 126:3097.
  23. Fihn SD, Blankenship JC, Alexander KP, et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2014; 64:1929.
  24. Morrow DA, Givertz MM. Modulation of myocardial energetics: emerging evidence for a therapeutic target in cardiovascular disease. Circulation 2005; 112:3218.
  25. Lee L, Horowitz J, Frenneaux M. Metabolic manipulation in ischaemic heart disease, a novel approach to treatment. Eur Heart J 2004; 25:634.
  26. Rosano GM, Marazzi G, Patrizi R, et al. Comparison of trimetazidine plus sildenafil to chronic nitrates in the control of myocardial ischemia during sexual activity in patients with coronary artery disease. Am J Cardiol 2005; 95:327.
  27. Szwed H, Sadowski Z, Elikowski W, et al. Combination treatment in stable effort angina using trimetazidine and metoprolol: results of a randomized, double-blind, multicentre study (TRIMPOL II). TRIMetazidine in POLand. Eur Heart J 2001; 22:2267.
  28. Ciapponi A, Pizarro R, Harrison J. Trimetazidine for stable angina. Cochrane Database Syst Rev 2005; :CD003614.
  29. White HD, Lowe JB. Antianginal efficacy of perhexiline maleate in patients refractory to beta-adrenoreceptor blockade. Int J Cardiol 1983; 3:145.
  30. Cole PL, Beamer AD, McGowan N, et al. Efficacy and safety of perhexiline maleate in refractory angina. A double-blind placebo-controlled clinical trial of a novel antianginal agent. Circulation 1990; 81:1260.
  31. IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial. Lancet 2002; 359:1269.
  32. Noman A, Ang DS, Ogston S, et al. Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial. Lancet 2010; 375:2161.
  33. Rajendra NS, Ireland S, George J, et al. Mechanistic insights into the therapeutic use of high-dose allopurinol in angina pectoris. J Am Coll Cardiol 2011; 58:820.
  34. Kinlay S, Behrendt D, Wainstein M, et al. Role of endothelin-1 in the active constriction of human atherosclerotic coronary arteries. Circulation 2001; 104:1114.
  35. Wenzel RR, Fleisch M, Shaw S, et al. Hemodynamic and coronary effects of the endothelin antagonist bosentan in patients with coronary artery disease. Circulation 1998; 98:2235.
  36. Kyriakides ZS, Kremastinos DT, Kolettis TM, et al. Acute endothelin-A receptor antagonism prevents normal reduction of myocardial ischemia on repeated balloon inflations during angioplasty. Circulation 2000; 102:1937.
  37. Fox K, Ford I, Steg PG, et al. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med 2014; 371:1091.
  38. Diaz A, Bourassa MG, Guertin MC, Tardif JC. Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery disease. Eur Heart J 2005; 26:967.
  39. Kolloch R, Legler UF, Champion A, et al. Impact of resting heart rate on outcomes in hypertensive patients with coronary artery disease: findings from the INternational VErapamil-SR/trandolapril STudy (INVEST). Eur Heart J 2008; 29:1327.
  40. Borer JS, Fox K, Jaillon P, et al. Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial. Circulation 2003; 107:817.
  41. Tardif JC, Ford I, Tendera M, et al. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J 2005; 26:2529.
  42. Tardif JC, Ponikowski P, Kahan T, ASSOCIATE Study Investigators. Efficacy of the I(f) current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial. Eur Heart J 2009; 30:540.
  43. Fox K, Ford I, Steg PG, et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet 2008; 372:807.
  44. Fox K, Ford I, Steg PG, et al. Relationship between ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial. Eur Heart J 2009; 30:2337.
  45. Mohri M, Shimokawa H, Hirakawa Y, et al. Rho-kinase inhibition with intracoronary fasudil prevents myocardial ischemia in patients with coronary microvascular spasm. J Am Coll Cardiol 2003; 41:15.
  46. Vicari RM, Chaitman B, Keefe D, et al. Efficacy and safety of fasudil in patients with stable angina: a double-blind, placebo-controlled, phase 2 trial. J Am Coll Cardiol 2005; 46:1803.
  47. Rosano GM, Leonardo F, Pagnotta P, et al. Acute anti-ischemic effect of testosterone in men with coronary artery disease. Circulation 1999; 99:1666.
  48. English KM, Steeds RP, Jones TH, et al. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study. Circulation 2000; 102:1906.
  49. van Ramshorst J, Bax JJ, Beeres SL, et al. Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA 2009; 301:1997.
  50. Pitt B, Waters D, Brown WV, et al. Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. Atorvastatin versus Revascularization Treatment Investigators. N Engl J Med 1999; 341:70.
  51. Deanfield JE, Sellier P, Thaulow E, et al. Potent anti-ischaemic effects of statins in chronic stable angina: incremental benefit beyond lipid lowering? Eur Heart J 2010; 31:2650.
  52. Arora RR, Chou TM, Jain D, et al. The multicenter study of enhanced external counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and anginal episodes. J Am Coll Cardiol 1999; 33:1833.
  53. Lawson WE, Hui JC, Lang G. Treatment benefit in the enhanced external counterpulsation consortium. Cardiology 2000; 94:31.
  54. Soran O, Kennard ED, Kfoury AG, et al. Two-year clinical outcomes after enhanced external counterpulsation (EECP) therapy in patients with refractory angina pectoris and left ventricular dysfunction (report from The International EECP Patient Registry). Am J Cardiol 2006; 97:17.
  55. Braith RW, Conti CR, Nichols WW, et al. Enhanced external counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic angina: a randomized sham-controlled study. Circulation 2010; 122:1612.
  56. Urano H, Ikeda H, Ueno T, et al. Enhanced external counterpulsation improves exercise tolerance, reduces exercise-induced myocardial ischemia and improves left ventricular diastolic filling in patients with coronary artery disease. J Am Coll Cardiol 2001; 37:93.
  57. Stys TP, Lawson WE, Hui JC, et al. Effects of enhanced external counterpulsation on stress radionuclide coronary perfusion and exercise capacity in chronic stable angina pectoris. Am J Cardiol 2002; 89:822.
  58. Shechter M, Matetzky S, Feinberg MS, et al. External counterpulsation therapy improves endothelial function in patients with refractory angina pectoris. J Am Coll Cardiol 2003; 42:2090.
  59. Akhtar M, Wu GF, Du ZM, et al. Effect of external counterpulsation on plasma nitric oxide and endothelin-1 levels. Am J Cardiol 2006; 98:28.
  60. Nichols WW, Estrada JC, Braith RW, et al. Enhanced external counterpulsation treatment improves arterial wall properties and wave reflection characteristics in patients with refractory angina. J Am Coll Cardiol 2006; 48:1208.
  61. www.cms.hhs.gov/mcd/viewncd.asp?ncd_id=20.20&ncd_version=2&basket=ncd%3A20%2E20%3A2%3AExternal+Counterpulsation+%28ECP%29+for+Severe+Angina (Accessed on August 01, 2006).
  62. Mannheimer C, Eliasson T, Augustinsson LE, et al. Electrical stimulation versus coronary artery bypass surgery in severe angina pectoris: the ESBY study. Circulation 1998; 97:1157.
  63. Norrsell H, Pilhall M, Eliasson T, Mannheimer C. Effects of spinal cord stimulation and coronary artery bypass grafting on myocardial ischemia and heart rate variability: further results from the ESBY study. Cardiology 2000; 94:12.
  64. McNab D, Khan SN, Sharples LD, et al. An open label, single-centre, randomized trial of spinal cord stimulation vs. percutaneous myocardial laser revascularization in patients with refractory angina pectoris: the SPiRiT trial. Eur Heart J 2006; 27:1048.
  65. Eckert S, Horstkotte D. Management of angina pectoris: the role of spinal cord stimulation. Am J Cardiovasc Drugs 2009; 9:17.
  66. Foreman RD, Linderoth B, Ardell JL, et al. Modulation of intrinsic cardiac neurons by spinal cord stimulation: implications for its therapeutic use in angina pectoris. Cardiovasc Res 2000; 47:367.
  67. Murray S, Collins PD, James MA. Neurostimulation treatment for angina pectoris. Heart 2000; 83:217.
  68. Leon MB, Kornowski R, Downey WE, et al. A blinded, randomized, placebo-controlled trial of percutaneous laser myocardial revascularization to improve angina symptoms in patients with severe coronary disease. J Am Coll Cardiol 2005; 46:1812.
  69. Lanza GA, Sestito A, Sgueglia GA, et al. Effect of spinal cord stimulation on spontaneous and stress-induced angina and 'ischemia-like' ST-segment depression in patients with cardiac syndrome X. Eur Heart J 2005; 26:983.
  70. Banai S, Ben Muvhar S, Parikh KH, et al. Coronary sinus reducer stent for the treatment of chronic refractory angina pectoris: a prospective, open-label, multicenter, safety feasibility first-in-man study. J Am Coll Cardiol 2007; 49:1783.
  71. Verheye S, Jolicœur EM, Behan MW, et al. Efficacy of a device to narrow the coronary sinus in refractory angina. N Engl J Med 2015; 372:519.