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Drug Therapy for Stable Angina Pectoris

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Abstract

Chronic stable angina pectoris refers to the predictable, reproducible occurrence of pressure or a choking sensation in the chest or adjacent areas caused by myocardial ischemia in association with physical or emotional stress, and cessation of exertion and or sublingual nitroglycerin invariably relieves the discomfort. It is a common presenting symptom of severe narrowing of one or more coronary arteries, non-obstructive coronary arteries, or even when the coronary arteries are angiographically normal. Patients often avoid activities which precipitate symptoms and have impaired quality of life. Most patients with angina pectoris can be managed with lifestyle changes, especially abstinence from smoking and regular exercise, and anti-anginal drugs. However, the choice of initial or combination antianginals as recommended in the guidelines is not evidence based. In addition, patients with stable angina due to coronary artery disease should also receive aspirin and a statin. Treatment of patients with angina and normal coronary arteries remains to be established. The aim of this article is to provide the readers not only with a guideline-based approach, which varies from one country to another, but also an individual-based approach, which takes into consideration circulatory status and the presence or absence of comorbidities in the treatment decision-making process. This manuscript primarily deals with drug therapy of stable angina pectoris and not coronary artery revascularization, which also provides angina relief but is usually reserved for patients who fail to respond to adequate drug therapy.

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References

  1. Heberden W. Some account of a disorder of the breast. Medical Tranasactions. Vol. 2. Royal College of Physicians. 1772.

  2. Opie LH. Angina pectoris: the evolution of concepts. J Cardiovasc Pharmacol Ther. 2004;9(Suppl 1):S3–9.

    Article  PubMed  Google Scholar 

  3. Abrams J, Thadani U. Therapy of stable angina pectoris: the uncomplicated patient. Circulation. 2005;112(15):e255–9. doi:10.1161/CIRCULATIONAHA.104.526699.

    Article  PubMed  Google Scholar 

  4. Thadani U. Current medical management of chronic stable angina. J Cardiovasc Pharmacol Ther. 2004;9(Suppl 1):S11–29 (quiz S98–9).

  5. Lucien C. Grading of angina pectoris. Circulation. 1976;54:522–3.

  6. Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, 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. J Am Coll Cardiol. 2012;60(24):e44–164. doi:10.1016/j.jacc.2012.07.013.

    Article  PubMed  Google Scholar 

  7. Thadani U. Management of stable angina-current guidelines: a critical apraisal. Cardiovasc Drugs Ther. 2016;30(4):419–26.

    Article  PubMed  Google Scholar 

  8. Task Force M, Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949–3003. doi:10.1093/eurheartj/eht296.

    Article  Google Scholar 

  9. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38–360. doi:10.1161/CIR.0000000000000350.

    Article  PubMed  Google Scholar 

  10. Incidence and prevalence: 2006 chart book on cardiovascular and lung diseases. Bethesda: National Heart, Lung, and Blood Institute; 2006.

  11. Javitz HS, Ward MM, Watson JB, Jaana M. Cost of illness of chronic angina. Am J Manag Care. 2004;10(11 Suppl):S358–69.

    PubMed  Google Scholar 

  12. Pocock SJ, Henderson RA, Clayton T, Lyman GH, Chamberlain DA. Quality of life after coronary angioplasty or continued medical treatment for angina: three-year follow-up in the RITA-2 trial. Randomized Intervention Treatment of Angina. J Am Coll Cardiol. 2000;35(4):907–14.

    Article  CAS  PubMed  Google Scholar 

  13. Hlatky MA, Rogers WJ, Johnstone I, Boothroyd D, Brooks MM, Pitt B, et al. Medical care costs and quality of life after randomization to coronary angioplasty or coronary bypass surgery. Bypass Angioplasty Revascularization Investigation (BARI) Investigators. N Engl J Med. 1997;336(2):92–9. doi:10.1056/NEJM199701093360203.

    Article  CAS  PubMed  Google Scholar 

  14. Thadani U. Chronic stable angina pectoris. In: M. C, editor. Cardiology. Philadelphia: Saunders Elsevier; 2010. p. 283–99.

  15. Rousan TA, Mathew ST, Thadani U. The risk of cardiovascular side effects with anti-anginal drugs. Expert Opin Drug Saf. 2016:1–15. doi:10.1080/14740338.2016.1238457.

  16. Vitale C, Spoletini I, Malorni W, Perrone-Filardi P, Volterrani M, Rosano GM. Efficacy of trimetazidine on functional capacity in symptomatic patients with stable exertional angina–the VASCO-angina study. Int J Cardiol. 2013;168(2):1078–81. doi:10.1016/j.ijcard.2012.11.001.

    Article  PubMed  Google Scholar 

  17. Sendon JL, Lee S, Cheng ML, Ben-Yehuda O, investigators Cs. 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. doi:10.1177/2047487312450133.

  18. Chaitman BR, Skettino SL, Parker JO, Hanley P, Meluzin J, Kuch J, 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. doi:10.1016/j.jacc.2003.11.045.

    Article  CAS  PubMed  Google Scholar 

  19. McClellan KJ, Plosker GL. Trimetazidine. A review of its use in stable angina pectoris and other coronary conditions. Drugs. 1999;58(1):143–57.

    Article  CAS  PubMed  Google Scholar 

  20. Huang HL, Fox KA. The impact of beta-blockers on mortality in stable angina: a meta-analysis. Scott Med J. 2012;57(2):69–75. doi:10.1258/smj.2011.011274.

    Article  CAS  PubMed  Google Scholar 

  21. Bangalore S, Steg G, Deedwania P, Crowley K, Eagle KA, Goto S, et al. beta-Blocker use and clinical outcomes in stable outpatients with and without coronary artery disease. JAMA. 2012;308(13):1340–9. doi:10.1001/jama.2012.12559.

    Article  CAS  PubMed  Google Scholar 

  22. Mancini GB, Gosselin G, Chow B, Kostuk W, Stone J, Yvorchuk KJ, et al. Canadian Cardiovascular Society guidelines for the diagnosis and management of stable ischemic heart disease. Can J Cardiol. 2014;30(8):837–49. doi:10.1016/j.cjca.2014.05.013.

    Article  PubMed  Google Scholar 

  23. Thadani U, Lipicky RJ. Short and long-acting oral nitrates for stable angina pectoris. Cardiovasc Drugs Ther. 1994;8(4):611–23.

    Article  CAS  PubMed  Google Scholar 

  24. Thadani U, Lipicky RJ. Ointments and transdermal nitroglycerin patches for stable angina pectoris. Cardiovasc Drugs Ther. 1994;8(4):625–33.

    Article  CAS  PubMed  Google Scholar 

  25. Heidenreich PA, McDonald KM, Hastie T, Fadel B, Hagan V, Lee BK, et al. Meta-analysis of trials comparing beta-blockers, calcium antagonists, and nitrates for stable angina. JAMA. 1999;281(20):1927–36.

    Article  CAS  PubMed  Google Scholar 

  26. Thadani U, Opie, LH. Nitrates. In: Opie, LH, editor. Drugs for the heart. Philadelphia: W. B. Saunders; 1995. p. 31-49.

  27. Thadani U. Challenges with nitrate therapy and nitrate tolerance: prevalence, prevention, and clinical relevance. Am J Cardiovasc Drugs. 2014;14(4):287–301. doi:10.1007/s40256-014-0072-5.

    Article  CAS  PubMed  Google Scholar 

  28. Munzel T, Daiber A, Gori T. Nitrate therapy: new aspects concerning molecular action and tolerance. Circulation. 2011;123(19):2132–44. doi:10.1161/CIRCULATIONAHA.110.981407.

    Article  PubMed  Google Scholar 

  29. Parker JO, Farrell B, Lahey KA, Moe G. Effect of intervals between doses on the development of tolerance to isosorbide dinitrate. N Engl J Med. 1987;316(23):1440–4. doi:10.1056/NEJM198706043162303.

    Article  CAS  PubMed  Google Scholar 

  30. Thadani U, Wittig T. A randomized, double-blind, placebo-controlled, crossover, dose-ranging multicenter study to determine the effect of sublingual nitroglycerin spray on exercise capacity in patients with chronic stable angina. Clin Med Insights Cardiol. 2012;6:87–95. doi:10.4137/CMC.S9132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Thadani U, Fung HL, Darke AC, Parker JO. Oral isosorbide dinitrate in angina pectoris: comparison of duration of action an dose-response relation during acute and sustained therapy. Am J Cardiol. 1982;49(2):411–9.

    Article  CAS  PubMed  Google Scholar 

  32. Bassan MM. The daylong pattern of the antianginal effect of long-term three times daily administered isosorbide dinitrate. J Am Coll Cardiol. 1990;16(4):936–40.

    Article  CAS  PubMed  Google Scholar 

  33. Fox KM, Dargie HJ, Deanfield J, Maseri A. Avoidance of tolerance and lack of rebound with intermittent dose titrated transdermal glyceryl trinitrate. The Transdermal Nitrate Investigators. Br Heart J. 1991;66(2):151–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Steering Committee, Transdermal Nitroglycerin Cooperative Study. Acute and chronic antianginal efficacy of continuous twenty-four-hour application of transdermal nitroglycerin. Am J Cardiol. 1991;68(13):1263–73.

  35. Chrysant SG, Glasser SP, Bittar N, Shahidi FE, Danisa K, Ibrahim R, et al. Efficacy and safety of extended-release isosorbide mononitrate for stable effort angina pectoris. Am J Cardiol. 1993;72(17):1249–56.

    Article  CAS  PubMed  Google Scholar 

  36. Thadani U, Rodgers T. Side effects of using nitrates to treat angina. Expert Opin Drug Saf. 2006;5(5):667–74. doi:10.1517/14740338.5.5.667.

    Article  CAS  PubMed  Google Scholar 

  37. Kloner RA. Cardiovascular effects of the 3 phosphodiesterase-5 inhibitors approved for the treatment of erectile dysfunction. Circulation. 2004;110(19):3149–55. doi:10.1161/01.CIR.0000146906.42375.D3.

    Article  PubMed  Google Scholar 

  38. Rosen RC, Kostis JB. Overview of phosphodiesterase 5 inhibition in erectile dysfunction. Am J Cardiol. 2003;92(9A):9M–18M.

    Article  CAS  PubMed  Google Scholar 

  39. Prichard BN, Owens CW. Mode of action of beta-adrenergic blocking drugs in hypertension. Clin Physiol Biochem. 1990;8(Suppl 2):1–10.

    CAS  PubMed  Google Scholar 

  40. Prichard BN. Beta-adrenergic receptor blocking drugs in angina pectoris. Drugs. 1974;7(1):55–84.

    Article  CAS  PubMed  Google Scholar 

  41. Thadani U, Davidson C, Singleton W, Taylor SH. Comparison of the immediate effects of five beta-adrenoreceptor-blocking drugs with different ancillary properties in angina pectoris. N Engl J Med. 1979;300(14):750–5. doi:10.1056/NEJM197904053001402.

    Article  CAS  PubMed  Google Scholar 

  42. Thadani U, Davidson C, Singleton W, Taylor SH. Comparison of five beta-adrenoreceptor antagonists with different ancillary properties during sustained twice daily therapy in angina pectoris. Am J Med. 1980;68(2):243–50.

    Article  CAS  PubMed  Google Scholar 

  43. Thadani U, Sharma B, Meeran MK, Majid PA, Whitaker W, Taylor SH. Comparison of adrenergic beta-receptor antagonists in angina pectoris. Br Med J. 1973;1(5846):138–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Opie LH, Sonnenblick EH, Frishman W, Thadani U. Beta blockers. Drugs for the heart. Philadelphia: W.B. Saunders; 1995, p. 1–27.

  45. Cruickshank JM. Measurement and cardiovascular relevance of partial agonist activity (PAA) involving beta 1- and beta 2-adrenoceptors. Pharmacol Ther. 1990;46(2):199–242.

    Article  CAS  PubMed  Google Scholar 

  46. McDevitt DG. Clinical significance of cardioselectivity state-of-the-art. Drugs. 1983;25(Supplemental 2):219–26.

  47. Prichard BN. Beta-blocking agents with vasodilating action. J Cardiovasc Pharmacol. 1992;19(Suppl 1):S1–4.

    Article  CAS  PubMed  Google Scholar 

  48. Kpaeyeh JA Jr, Wharton JM. Sotalol. Card Electrophysiol Clin. 2016;8(2):437–52. doi:10.1016/j.ccep.2016.02.007.

    Article  PubMed  Google Scholar 

  49. CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353(9146):9–13.

  50. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353(9169):2001–7.

  51. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334(21):1349–55. doi:10.1056/NEJM199605233342101.

    Article  CAS  PubMed  Google Scholar 

  52. Beta-Blocker Heart Attack Study Group. The beta-blocker heart attack trial. JAMA. 1981;246(18):2073–4.

  53. Hjalmarson A, Herlitz J, Holmberg S, Ryden L, Swedberg K, Vedin A, et al. The Goteborg metoprolol trial. Effects on mortality and morbidity in acute myocardial infarction. Circulation. 1983;67(6 Pt 2):I26–32.

  54. Bangalore S, Bhatt DL, Steg PG, Weber MA, Boden WE, Hamm CW, et al. beta-blockers and cardiovascular events in patients with and without myocardial infarction: post hoc analysis from the CHARISMA trial. Circ Cardiovasc Qual Outcomes. 2014;7(6):872–81. doi:10.1161/CIRCOUTCOMES.114.001073.

    Article  PubMed  Google Scholar 

  55. Bangalore S, Makani H, Radford M, Thakur K, Toklu B, Katz SD, et al. Clinical outcomes with beta-blockers for myocardial infarction: a meta-analysis of randomized trials. Am J Med. 2014;127(10):939–53. doi:10.1016/j.amjmed.2014.05.032.

    Article  CAS  PubMed  Google Scholar 

  56. Manolis AJ, Poulimenos LE, Ambrosio G, Kallistratos MS, Lopez-Sendon J, Dechend R, et al. Medical treatment of stable angina: a tailored therapeutic approach. Int J Cardiol. 2016;220:445–53. doi:10.1016/j.ijcard.2016.06.150.

    Article  PubMed  Google Scholar 

  57. Thadani U. Assessment of “optimal” beta blockade in treating patients with angina pectoris. Acta Med Scand Suppl. 1985;694:178–87.

    CAS  PubMed  Google Scholar 

  58. Goodman & Gilman’s Pharmacological Basis of Therapeutics. Brunton L, Chabner B, Knollmann B, Editors. 12th ed. New York: McGraw-Hill; 2011

  59. Cordero A, Bertomeu-Gonzalez V, Mazon P, Moreno-Arribas J, Facila L, Bueno H, et al. Differential effect of beta-blockers for heart rate control in coronary artery disease. Clin Cardiol. 2011;34(12):748–54. doi:10.1002/clc.20981.

    Article  PubMed  Google Scholar 

  60. Greenblatt DJK-WJ. Clinical toxicity of propranolol and practolol: a report from the Boston Collaborative Drug Surveillance Program. Cardiovascualr drugs. Sydney: Adis Press; 1977.

    Google Scholar 

  61. Opie LH, Gersh BJ. Drugs for the heart. 8th ed. Philadelphia: Elsevier Saunders; 2013.

    Google Scholar 

  62. Husted SE, Ohman EM. Pharmacological and emerging therapies in the treatment of chronic angina. Lancet. 2015;386(9994):691–701. doi:10.1016/S0140-6736(15)61283-1.

    Article  CAS  PubMed  Google Scholar 

  63. Abernethy DR, Schwartz JB. Calcium-antagonist drugs. N Engl J Med. 1999;341(19):1447–57. doi:10.1056/NEJM199911043411907.

    Article  CAS  PubMed  Google Scholar 

  64. Freher M, Challapalli S, Pinto JV, Schwartz J, Bonow RO, Gheorgiade M. Current status of calcium channel blockers in patients with cardiovascular disease. Curr Probl Cardiol. 1999;24(5):236–340.

    Article  CAS  PubMed  Google Scholar 

  65. Singh BN, Ellrodt G, Peter CT. Verapamil: a review of its pharmacological properties and therapeutic use. Drugs. 1978;15(3):169–97.

    Article  PubMed  Google Scholar 

  66. Chaffman M, Brogden RN. Diltiazem. A review of its pharmacological properties and therapeutic efficacy. Drugs. 1985;29(5):387–454.

    Article  CAS  PubMed  Google Scholar 

  67. Ezekowitz MD, Hossack K, Mehta JL, Thadani U, Weidler DJ, Kostuk W, et al. Amlodipine in chronic stable angina: results of a multicenter double-blind crossover trial. Am Heart J. 1995;129(3):527–35.

    Article  CAS  PubMed  Google Scholar 

  68. Glasser SP, West TW. Clinical safety and efficacy of once-a-day amlodipine for chronic stable angina pectoris. Am J Cardiol. 1988;62(9):518–22.

    Article  CAS  PubMed  Google Scholar 

  69. Thadani U, Glasser S, Bittar N, Beach CL. Dose-response evaluation of once-daily therapy with a new formulation of diltiazem for stable angina pectoris. Diltiazem CD Study Group. Am J Cardiol. 1994;74(1):9–17.

    Article  CAS  PubMed  Google Scholar 

  70. Rehnqvist N, Hjemdahl P, Billing E, Bjorkander I, Eriksson SV, Forslund L, et al. Treatment of stable angina pectoris with calcium antagonists and beta-blockers. The APSIS study. Angina Prognosis Study in Stockholm. Cardiologia. 1995;40(12 Suppl 1):301.

  71. Hauf-Zachariou U, Blackwood RA, Gunawardena KA, O’Donnell JG, Garnham S, Pfarr E. Carvedilol versus verapamil in chronic stable angina: a multicentre trial. Eur J Clin Pharmacol. 1997;52(2):95–100.

    Article  CAS  PubMed  Google Scholar 

  72. Poole-Wilson PA, Lubsen J, Kirwan BA, van Dalen FJ, Wagener G, Danchin N, et al. Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial. Lancet. 2004;364(9437):849–57. doi:10.1016/S0140-6736(04)16980-8.

    Article  CAS  PubMed  Google Scholar 

  73. Sierra C, Coca A. The ACTION study: nifedipine in patients with symptomatic stable angina and hypertension. Expert Rev Cardiovasc Ther. 2008;6(8):1055–62. doi:10.1586/14779072.6.8.1055.

    Article  CAS  PubMed  Google Scholar 

  74. Van Der Vring JA, Daniels MC, Holwerda NJ, Withagen PJ, Schelling A, Cleophas TJ, et al. Combination of calcium channel blockers and beta-adrenoceptor blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. Netherlands Working Group on Cardiovascular Research (WCN). Br J Clin Pharmacol. 1999;47(5):493–8.

  75. Antman E, Muller J, Goldberg S, MacAlpin R, Rubenfire M, Tabatznik B, et al. Nifedipine therapy for coronary-artery spasm. Experience in 127 patients. N Engl J Med. 1980;302(23):1269–73. doi:10.1056/NEJM198006053022301.

    Article  CAS  PubMed  Google Scholar 

  76. Pepine CJ, Feldman RL, Whittle J, Curry RC, Conti CR. Effect of diltiazem in patients with variant angina: a randomized double-blind trial. Am Heart J. 1981;101(6):719–25.

    Article  CAS  PubMed  Google Scholar 

  77. The Multicenter Diltiazem Postinfarction Trial Research Group. The effect of diltiazem on mortality and reinfarction after myocardial infarction. N Engl J Med. 1988;319(7):385–92. doi:10.1056/NEJM198808183190701.

  78. Krebs R. Adverse reactions with calcium antagonists. Hypertension. 1983;5(4 Pt 2):II125–9.

  79. Nicorandil for angina. Drug Ther Bull. 1995;33(12):89–92.

  80. Camm AJ, Maltz MB. A controlled single-dose study of the efficacy, dose response and duration of action of nicorandil in angina pectoris. Am J Cardiol. 1989;63(21):61J–5J.

    Article  CAS  PubMed  Google Scholar 

  81. Group IS. Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial. Lancet. 2002;359(9314):1269–75. doi:10.1016/S0140-6736(02)08265-X.

    Article  Google Scholar 

  82. Thadani U. Can nicorandil treat angina pectoris effectively? Nature clinical practice. Cardiovasc Med. 2005;2(4):186–7. doi:10.1038/ncpcardio0159.

    CAS  Google Scholar 

  83. DiFrancesco D. Pacemaker mechanisms in cardiac tissue. Annu Rev Physiol. 1993;55:455–72. doi:10.1146/annurev.ph.55.030193.002323.

    Article  CAS  PubMed  Google Scholar 

  84. Borer JS, Fox K, Jaillon P, Lerebours G, Ivabradine Investigators G. Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial. Circulation. 2003;107(6):817–23.

    Article  PubMed  Google Scholar 

  85. Ferrari R, Ceconi C. Selective and specific I(f) inhibition with ivabradine: new perspectives for the treatment of cardiovascular disease. Expert Rev Cardiovasc Ther. 2011;9(8):959–73. doi:10.1586/erc.11.99.

    Article  PubMed  Google Scholar 

  86. Colin P, Ghaleh B, Monnet X, Su J, Hittinger L, Giudicelli JF, et al. Contributions of heart rate and contractility to myocardial oxygen balance during exercise. Am J Physiol Heart Circ Physiol. 2003;284(2):H676–82. doi:10.1152/ajpheart.00564.2002.

    Article  CAS  PubMed  Google Scholar 

  87. Joannides R, Moore N, Iacob M, Compagnon P, Lerebours G, Menard JF, et al. Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise. Br J Clin Pharmacol. 2006;61(2):127–37. doi:10.1111/j.1365-2125.2005.02544.x.

    Article  CAS  PubMed  Google Scholar 

  88. Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K, Investigators I. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J. 2005;26(23):2529–36. doi:10.1093/eurheartj/ehi586.

    Article  CAS  PubMed  Google Scholar 

  89. Tardif JC, Ponikowski P, Kahan T, Investigators AS. 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(5):540–8. doi:10.1093/eurheartj/ehn571.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Werdan K, Ebelt H, Nuding S, Hopfner F, Hack G, Muller-Werdan U. Ivabradine in combination with beta-blocker improves symptoms and quality of life in patients with stable angina pectoris: results from the ADDITIONS study. Clin Res Cardiol. 2012;101(5):365–73. doi:10.1007/s00392-011-0402-4.

    Article  CAS  PubMed  Google Scholar 

  91. Koster R, Kaehler J, Meinertz T, Group RS. Treatment of stable angina pectoris by ivabradine in every day practice: the REDUCTION study. Am Heart J. 2009;158(4):e51–7. doi:10.1016/j.ahj.2009.06.008.

    Article  PubMed  CAS  Google Scholar 

  92. Muller-Werdan U, Stockl G, Ebelt H, Nuding S, Hopfner F, Werdan K, et al. Ivabradine in combination with beta-blocker reduces symptoms and improves quality of life in elderly patients with stable angina pectoris: age-related results from the ADDITIONS study. Exp Gerontol. 2014;59:34–41. doi:10.1016/j.exger.2014.09.002.

    Article  PubMed  CAS  Google Scholar 

  93. Fox K, Ford I, Steg PG, Tendera M, Ferrari R, Investigators B. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9641):807–16. doi:10.1016/S0140-6736(08)61170-8.

    Article  CAS  PubMed  Google Scholar 

  94. Fox K, Ford I, Steg PG, Tendera M, Robertson M, Ferrari R, 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(19):2337–45. doi:10.1093/eurheartj/ehp358.

    Article  CAS  PubMed  Google Scholar 

  95. Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R, et al. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med. 2014;371(12):1091–9. doi:10.1056/NEJMoa1406430.

    Article  PubMed  CAS  Google Scholar 

  96. Swedberg K, Komajda M, Bohm M, Borer JS, Ford I, Dubost-Brama A, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376(9744):875–85. doi:10.1016/S0140-6736(10)61198-1.

    Article  CAS  PubMed  Google Scholar 

  97. Amgen, Inc. Ivabradine: highlights of prescribing information. 2015.

  98. Cocco G, Rousseau MF, Bouvy T, Cheron P, Williams G, Detry JM, et al. Effects of a new metabolic modulator, ranolazine, on exercise tolerance in angina pectoris patients treated with beta-blocker or diltiazem. J Cardiovasc Pharmacol. 1992;20(1):131–8.

    CAS  PubMed  Google Scholar 

  99. Anderson JR, Khou S, Nawarskas JJ. Ranolazine: a potential new treatment for chronic stable angina. Heart Dis. 2001;3(4):263–9.

    Article  CAS  PubMed  Google Scholar 

  100. 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 (British Cardiac Society). 2006;92 Suppl 4:iv6–14. doi:10.1136/hrt.2005.078790.

  101. Thadani U. Should ranolazine be used for all patients with ischemic heart disease or only for symptomatic patients with stable angina or for those with refractory angina pectoris? A critical appraisal. Expert Opin Pharmacother. 2012;13(17):2555–63. doi:10.1517/14656566.2012.740458.

    Article  CAS  PubMed  Google Scholar 

  102. Codolosa JN, Acharjee S, Figueredo VM. Update on ranolazine in the management of angina. Vasc Health Risk Manag. 2014;10:353–62. doi:10.2147/VHRM.S40477.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Thadani U, Ezekowitz M, Fenney L, Chiang YK. Double-blind efficacy and safety study of a novel anti-ischemic agent, ranolazine, versus placebo in patients with chronic stable angina pectoris. Ranolazine Study Group. Circulation. 1994;90(2):726–34.

    Article  CAS  PubMed  Google Scholar 

  104. 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;84(1):46–50.

  105. Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J, 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. doi:10.1001/jama.291.3.309.

    Article  CAS  PubMed  Google Scholar 

  106. Kosiborod M, Arnold SV, Spertus JA, McGuire DK, Li Y, Yue P, 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(20):2038–45. doi:10.1016/j.jacc.2013.02.011.

    Article  CAS  PubMed  Google Scholar 

  107. Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L, Investigators E. 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. doi:10.1016/j.jacc.2006.05.044.

    Article  CAS  PubMed  Google Scholar 

  108. Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S, 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. doi:10.1001/jama.297.16.1775.

    Article  CAS  PubMed  Google Scholar 

  109. Bairey Merz CN, Handberg EM, Shufelt CL, Mehta PK, Minissian MB, Wei J, et al. A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve. Eur Heart J. 2016;37(19):1504–13. doi:10.1093/eurheartj/ehv647.

    Article  PubMed  Google Scholar 

  110. Weisz G, Farzaneh-Far R, Ben-Yehuda O, Debruyne B, Montalescot G, Lerman A, et al. Use of ranolazine in patients with incomplete revascularization after percutaneous coronary intervention: design and rationale of the Ranolazine for Incomplete Vessel Revascularization Post-Percutaneous Coronary Intervention (RIVER-PCI) trial. Am Heart J. 2013;166(6):953–9 e3. doi:10.1016/j.ahj.2013.08.004.

  111. Gilead Sciences, Inc. Ranolazine prescribing information. 2016.

  112. Gupta AK, Winchester D, Pepine CJ. Antagonist molecules in the treatment of angina. Expert Opin Pharmacother. 2013;14(17):2323–42. doi:10.1517/14656566.2013.834329.

    Article  CAS  PubMed  Google Scholar 

  113. Thadani U. Modified-release formulation of trimetazidine for exceptional control of angina pectoris: fact or fiction. Am J Cardiovasc Drugs. 2005;5(5):331–4.

    Article  CAS  PubMed  Google Scholar 

  114. Szwed H, Pachocki R, Domzal-Bochenska M, Szymczak K, Szydlowski Z, Paradowski A, et al. Efficacy and tolerance of trimetazidine, a metabolic antianginal, in combination with a hemodynamic antianginal in stable exertion angina. TRIMPOL I, a multicenter study. Presse Med. 2000;29(10):533–8.

    CAS  PubMed  Google Scholar 

  115. Szwed H, Sadowski Z, Elikowski W, Koronkiewicz A, Mamcarz A, Orszulak 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(24):2267–74. doi:10.1053/euhj.2001.2896.

    Article  CAS  PubMed  Google Scholar 

  116. Peng S, Zhao M, Wan J, Fang Q, Fang D, Li K. The efficacy of trimetazidine on stable angina pectoris: a meta-analysis of randomized clinical trials. Int J Cardiol. 2014;177(3):780–5. doi:10.1016/j.ijcard.2014.10.149.

    Article  PubMed  Google Scholar 

  117. Dalla-Volta S, Maraglino G, Della-Valentina P, Viena P, Desideri A. Comparison of trimetazidine with nifedipine in effort angina: a double-blind, crossover study. Cardiovasc Drugs Ther. 1990;4(Suppl 4):853–9.

    Article  PubMed  Google Scholar 

  118. Reversible Parkinsonism linked to trimetazidine (continued). Prescrire Int. 2006;15(84):136.

  119. Marti Masso JF, Marti I, Carrera N, Poza JJ, Lopez de Munain A. Trimetazidine induces parkinsonism, gait disorders and tremor. Therapie. 2005;60(4):419–22.

    Article  PubMed  Google Scholar 

  120. Masmoudi K, Masson H, Gras V, Andrejak M. Extrapyramidal adverse drug reactions associated with trimetazidine: a series of 21 cases. Fundam Clin Pharmacol. 2012;26(2):198–203. doi:10.1111/j.1472-8206.2011.01008.x.

    Article  CAS  PubMed  Google Scholar 

  121. European Medicines Agency. European Medicines Agency recommends restricting use of trimetazidine-containing medicines. 22 June 2012.

  122. Vicari RM, Chaitman B, Keefe D, Smith WB, Chrysant SG, Tonkon MJ, 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(10):1803–11. doi:10.1016/j.jacc.2005.07.047.

    Article  CAS  PubMed  Google Scholar 

  123. Pepine CJ, Rouleau JL, Annis K, Ducharme A, Ma P, Lenis J, et al. Effects of angiotensin-converting enzyme inhibition on transient ischemia: the Quinapril Anti-Ischemia and Symptoms of Angina Reduction (QUASAR) trial. J Am Coll Cardiol. 2003;42(12):2049–59.

    Article  CAS  PubMed  Google Scholar 

  124. Heart Protection Study Collaborative G. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7–22. doi:10.1016/S0140-6736(02)09327-3.

    Article  Google Scholar 

  125. Kelkar A, Kuo A, Frishman WH. Allopurinol as a cardiovascular drug. Cardiol Rev. 2011;19(6):265–71. doi:10.1097/CRD.0b013e318229a908.

    Article  PubMed  Google Scholar 

  126. Day RO, Graham GG, Hicks M, McLachlan AJ, Stocker SL, Williams KM. Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Clin Pharmacokinet. 2007;46(8):623–44. doi:10.2165/00003088-200746080-00001.

    Article  CAS  PubMed  Google Scholar 

  127. Spiekermann S, Landmesser U, Dikalov S, Bredt M, Gamez G, Tatge H, et al. Electron spin resonance characterization of vascular xanthine and NAD(P)H oxidase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation. 2003;107(10):1383–9.

    Article  CAS  PubMed  Google Scholar 

  128. Stone PH. Allopurinol a new anti-ischemic role for an old drug. J Am Coll Cardiol. 2011;58(8):829–30. doi:10.1016/j.jacc.2011.02.072.

    Article  PubMed  Google Scholar 

  129. George J, Carr E, Davies J, Belch JJ, Struthers A. High-dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not by lowering uric acid. Circulation. 2006;114(23):2508–16. doi:10.1161/CIRCULATIONAHA.106.651117.

    Article  CAS  PubMed  Google Scholar 

  130. Rekhraj S, Gandy SJ, Szwejkowski BR, Nadir MA, Noman A, Houston JG, et al. High-dose allopurinol reduces left ventricular mass in patients with ischemic heart disease. J Am Coll Cardiol. 2013;61(9):926–32. doi:10.1016/j.jacc.2012.09.066.

    Article  CAS  PubMed  Google Scholar 

  131. Devereux RB, Wachtell K, Gerdts E, Boman K, Nieminen MS, Papademetriou V, et al. Prognostic significance of left ventricular mass change during treatment of hypertension. JAMA. 2004;292(19):2350–6. doi:10.1001/jama.292.19.2350.

    Article  CAS  PubMed  Google Scholar 

  132. Noman A, Ang DS, Ogston S, Lang CC, Struthers AD. Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial. Lancet. 2010;375(9732):2161–7. doi:10.1016/S0140-6736(10)60391-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Dunselman PH, van Kempen LH, Bouwens LH, Holwerda KJ, Herweijer AH, Bernink PJ. Value of the addition of amlodipine to atenolol in patients with angina pectoris despite adequate beta blockade. Am J Cardiol. 1998;81(2):128–32.

    Article  CAS  PubMed  Google Scholar 

  134. Rousseau MF, Pouleur H, Cocco G, Wolff AA. Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris. Am J Cardiol. 2005;95(3):311–6. doi:10.1016/j.amjcard.2004.09.025.

    Article  CAS  PubMed  Google Scholar 

  135. Critchley JA, Unal B. Is smokeless tobacco a risk factor for coronary heart disease? A systematic review of epidemiological studies. Eur J Cardiovasc Prev Rehabil. 2004;11(2):101–12.

    Article  PubMed  Google Scholar 

  136. Hambrecht R, Walther C, Mobius-Winkler S, Gielen S, Linke A, Conradi K, et al. Percutaneous coronary angioplasty compared with exercise training in patients with stable coronary artery disease: a randomized trial. Circulation. 2004;109(11):1371–8. doi:10.1161/01.CIR.0000121360.31954.1F.

    Article  PubMed  Google Scholar 

  137. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet. 1988;2(8607):349–60.

  138. Antithrombotic Trialists C, Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849–60. doi:10.1016/S0140-6736(09)60503-1.

    Article  CAS  Google Scholar 

  139. Juul-Moller S, Edvardsson N, Jahnmatz B, Rosen A, Sorensen S, Omblus R. Double-blind trial of aspirin in primary prevention of myocardial infarction in patients with stable chronic angina pectoris. The Swedish Angina Pectoris Aspirin Trial (SAPAT) Group. Lancet. 1992;340(8833):1421–5.

    Article  CAS  PubMed  Google Scholar 

  140. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354(16):1706–17. doi:10.1056/NEJMoa060989.

    Article  CAS  PubMed  Google Scholar 

  141. LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425–35. doi:10.1056/NEJMoa050461.

    Article  CAS  PubMed  Google Scholar 

  142. Investigators A-H, Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–67. doi:10.1056/NEJMoa1107579.

    Article  CAS  Google Scholar 

  143. Group AS, Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd, Leiter LA, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563–74. doi:10.1056/NEJMoa1001282.

  144. Group AS, Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575–85. doi:10.1056/NEJMoa1001286.

  145. Group SR, Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103–16. doi:10.1056/NEJMoa1511939.

  146. Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR, Lasser NL, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349(6):523–34. doi:10.1056/NEJMoa030808.

    Article  CAS  PubMed  Google Scholar 

  147. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med. 1987;316(23):1429–35. doi:10.1056/NEJM198706043162301.

  148. McMurray JJ, Ostergren J, Swedberg K, Granger CB, Held P, Michelson EL, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet. 2003;362(9386):767–71. doi:10.1016/S0140-6736(03)14283-3.

    Article  CAS  PubMed  Google Scholar 

  149. Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med. 1992;327(10):669–77. doi:10.1056/NEJM199209033271001.

    Article  CAS  PubMed  Google Scholar 

  150. Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344(22):1651–8. doi:10.1056/NEJM200105313442201.

    Article  CAS  PubMed  Google Scholar 

  151. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001;357(9266):1385–90.

    Article  CAS  PubMed  Google Scholar 

  152. Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, Komajda M, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet. 2003;362(9377):7–13. doi:10.1016/S0140-6736(03)13800-7.

    Article  CAS  PubMed  Google Scholar 

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  1. The University of Oklahoma Health Sciences Center and The Veteran Affairs Medical Center, 920 Stanton L. Young Blvd., WP 3010, Oklahoma City, OK, 73104, USA

    Talla A. Rousan, Sunil T. Mathew & Udho Thadani

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Dr. Udho Thadani received honoraria for consulting from Clovis Pharmaceuticals and Gilead Sciences; from the speakers’ bureau of Gilead Sciences and Amgen, and received research grants and is the local principal investigator for NIH and VA Coop studies and for multicenter trials with AstraZeneca and Novartis. Dr. Talla Rousan and Dr. Sunil Mathew declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Rousan, T.A., Mathew, S.T. & Thadani, U. Drug Therapy for Stable Angina Pectoris. Drugs 77, 265–284 (2017). https://doi.org/10.1007/s40265-017-0691-7

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