Ischaemic heart disease is a major cause of death and disability worldwide, while angina represents its most common symptom. It is estimated that approximately 9 million patients in the USA suffer from angina and its treatment is challenging, thus the strategy to improve the management of chronic stable angina is a priority. Angina might be the result of different pathologies, ranging from the “classical” obstruction of a large coronary artery to alteration of the microcirculation or coronary artery spasm. Current clinical guidelines recommend antianginal therapy to control symptoms, before considering coronary artery revascularization. In the current guidelines, drugs are classified as being first-choice (beta-blockers, calcium channel blockers, and short-acting nitrates) or second-choice (ivabradine, nicorandil, ranolazine, trimetazidine) treatment, with the recommendation to reserve second-line modifications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. However, such a categorical approach is currently questioned. In addition, current guidelines provide few suggestions to guide the choice of drugs more suitable according to the underlying pathology or the patient comorbidities. Several other questions have recently emerged, such as: is there evidence-based data between first- and second-line treatments in terms of prognosis or symptom relief? Actually, it seems that newer antianginal drugs, which are classified as second choice, have more evidence-based clinical data that are more contemporary to support their use than what is available for the first-choice drugs. It follows that actual guidelines are based more on tradition than on evidence and there is a need for new algorithms that are more individualized to patients, their comorbidities, and pathophysiological mechanism of chronic stable angina.

1.
Task Force Members, Montalescot G, Sechtem U, 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: 2949–3003.
2.
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. J Am Coll Cardiol 2012; 60:e44–e164.
3.
Mancini GB, Gosselin G, Chow B, et al: Canadian Cardiovascular Society guidelines for the diagnosis and management of stable ischemic heart disease. Can J Cardiol 2014; 30: 837–849.
4.
National Clinical Guidelines Centre: Stable angina: full guideline: methods, evidence and guidance. 2011. http://www.nice.org.uk/guidance/cg126/evidence/full-guideline-183176605 (accessed Dec 9, 2015).
5.
Abrams J: Clinical practice: chronic stable angina. N Engl J Med 2005; 352: 2524–2533.
6.
Gould KL, Lipscomb K: Effects of coronary stenoses on coronary flow reserve and resistance. Am J Cardiol 1974; 34: 48–55.
7.
Paul TK, Sivanesan K, Schulman-Marcus J: Sex differences in nonobstructive coronary artery disease: recent insights and substantial knowledge gaps. Trends Cardiovasc Med 2016; 27: 173–179.
8.
Marzilli M, Merz CN, Boden WE, Bonow RO, Capozza PG, Chilian WM, DeMaria AN, Guarini G, Huqi A, Morrone D, Patel MR, Weintraub WS: Obstructive coronary atherosclerosis and ischemic heart disease: an elusive link! J Am Coll Cardiol 2012; 60: 951–956.
9.
Lanza GA, Careri G, Crea F: Mechanisms of coronary artery spasm. Circulation 2011; 124: 1774–1782.
10.
Crea F, Camici PG, Bairey Merz CN: Coronary microvascular dysfunction: an update. Eur Heart J 2014; 35: 1101–1111.
11.
Sedlak T, Izadnegahdar M, Humphries KH, Bairey Merz CN: Sex-specific factors in microvascular angina. Can J Cardiol 2014; 30: 747–755.
12.
Coronary Artery Surgery Study (CASS): A randomized trial of coronary artery bypass surgery: survival data. Circulation 1983; 68: 939–950.
13.
Stergiopoulos K, Boden WE, Hartigan P, Möbius-Winkler S, Hambrecht R, Hueb W, Hardison RM, Abbott JD, Brown DL: Percutaneous coronary intervention outcomes in patients with stable obstructive coronary artery disease and myocardial ischemia: a collaborative meta-analysis of contemporary randomized clinical trials. JAMA Intern Med 2014; 174: 232–240.
14.
Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ; CANTOS Trial Group: Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017; 377: 1119–1131.
15.
Thadani U: Management of stable angina – current guidelines: a critical appraisal. Cardiovasc Drugs Ther 2016; 30: 419–426.
16.
Camm AJ, Manolis A, Ambrosio G, et al: Unresolved issues in the management of chronic stable angina. Int J Cardiol 2015; 201: 200–207.
17.
Ambrosio G, Komajda M, Mugelli A, et al: Management of stable angina: a commentary on the European Society of Cardiology guidelines. Eur J Prev Cardiol 2016; 23: 1401–1412.
18.
Ferrari R, Camici PG, Crea F, Danchin N, Fox K, Maggioni AP, Manolis A, Marzilli M, Rosano GMC, Lopez-Sendon JL: Expert consensus document: a “diamond” approach to personalized treatment of angina. Nat Rev Cardiol 2018; 15: 120–132.
19.
Heberden W: Some account of a disorder of the breast. Medical transitions. Royal College of Physiscians, 1772.
20.
David AR, Kershaw A, Heagarty: Atherosclerosis and diet in ancient Egypt. Lancet 2010; 375; 718–719.
21.
Gelb BD: History of our understanding of the causes of congenital heart disease. Circ Cardiovasc Genet 2015; 8: 529–536.
22.
Murrel W: Nitro-glycerine in angina pectoris. Lancet 1879; 1: 80–81.
23.
Black JW, Duncan WA, Shanks RG: Comparison of some properties of pronethalol and propranolol. Br J Pharmacol Chemother 1965; 25: 577–591.
24.
Fleckeinstain A: History of calcium antagonists. Circ Res 1983; 52: 469–125.
25.
Maddox TM, Reid KJ, Spertus JA, et al: Angina at 1 year after myocardial infarction: prevalence and associated findings. Arch Intern Med 2008; 168: 1310–1316.
26.
Hemingway H, Lanfenberg C, Damant J, Frost C, Pyörälä K, Barrett-Conor E: Prevalence of angina in women versus men: a systematic review and meta-analysis of international variations across 31 countries. Circulation 2008; 117: 1526–1536.
27.
Rossi R, Nuzzo A, Origliani G, Modena MG: Prognostic role of flow- mediated dilation and cardiac risk factors in post-menopausal women. J Am Coll Cardiol 2008; 51: 997–1002.
28.
Wilson PW, D’Agostino RB, Sullivan L, Parise H, Kannel WB: Over-weight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med 2002; 162: 1867–1872.
29.
Roger VL, Go AS, Lloyd-Jones DM, et al: Heart disease and stroke statistics – 2012 update: a report from the American Heart Association. Circulation 2012; 125:e2–e220.
30.
Feldman DN, Gade CL, Slotwiner AJ, et al: Comparison of outcomes of percutaneous coronary interventions in patients of three age groups (< 60, 60 to 80, and > 80 years) (from the New York State Angio-Plasty Registry). Am J Cardiol 2006; 98: 1334–1339.
31.
National Institutes of Health, National Heart, Lung, and Blood Institute: Morbidity and Mortality: 2012 Chart Book on Cardiovascular, Lung, Blood Diseases. Bethesda, NIH/National Heart, Lung, and Blood Institute, 2012.
32.
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK: Heart disease and stroke statistics – 2015 update: a report from the American Heart Association. Circulation 2015; 131:e29–e322.
33.
National Institutes of Health, National Heart, Lung, and Blood Institute: Incidence and Prevalence: 2006 Chart Book on Cardiovascular and Lung Diseases. Bethesda, NIH/National Heart, Lung, and Blood Institute, 2006.
34.
Rousan TA, Mathew ST, Thadani U: Drug therapy for stable angina pectoris. Drugs 2017; 77: 265–284.
35.
Pocock SJ, Henderson SA, Clayton T, Lyman GH, Chamberlain DA: Quality of life after coronary angioplasty or continued medical treatment for angina: three-year follow-up in the RITE-2 trial: randomized intervention treatment of Angina. J Am Coll Cardiol 2000; 35: 907–914.
36.
Tendera M, Chassany O, Ferrari R, Ford I, Steg PG, Tardif JC, Fox K: Quality of life with ivabradine in patients with angina pectoris: the study assessing the morbidity-mortality benefits of the if inhibitor ivabradine in patients with coronary artery disease quality of life substudy. Circ Cardiovasc Qual Outcomes 2016; 9: 31–38.
37.
Javitz HS, Ward MM, Watson JB, Jaana M: Cost of illness of chronic angina. Am J Manag Care 2004; 10(11 suppl):S358–S369.
38.
Epstein SE, Cannon RO 3rd: Site of increased resistance to coronary flow in patients with angina pectoris and normal epicardial coronary arteries. J Am Coll Cardiol 1986; 8: 459–461.
39.
Ferrari R: Coronary artery disease in 2012: revising common beliefs in the management of stable CAD. Nat Rev Cardiol 2013; 10: 65–66.
40.
Ferrari R, Nesta F, Boraso A: Increased heart rate is detrimental: the myocardial metabolic theory. Eur Heart J Suppl 1999; 1(H): 24–28.
41.
Nayler WG, Ferrari R, Poole-Wilson PA, Yepez CE: A protective effect of a mild acidosis an hypoxic heart muscle. J Mol Cell Cardiol 1979; 11: 1053–1071.
42.
Visioli O, Cucchini F, Bolognesi R, Raddino R, Di Lisa F, Ferrari R: Reproducibility of metabolic parameters during atrial pacing stress in cad patients. J Mol Cell Cardiol 1981; 13: 96.
43.
Sylven C: Mechanism of pain in angina pectoris: a critical review of the adenosine hypothesis. Cardiovasc Drugs Ther 1993; 7: 745–759.
44.
Crea F, Gaspardone A: New look at an old symptom: angina pectoris circulation. Circulation 1997; 96: 3766–3773.
45.
Braunwald E, Sobel B: Coronary blood flow and myocardial ischemia; in Braunwald E (ed): Heart Disease and Textbook of Cardiovascular Medicine. Philadelphia, WB Saunders, 1998, p 1191.
46.
Ferrari R, Balla C, Malagù M, Guardigli G, Morciano G, Bertini M, Biscaglia S, Campo G: Reperfusion Damage – A Story of Success, Failure, and Hope. Circ J 2017; 81: 131–141.
47.
Levine GN, Bates ER, Blankenship JC, et al: 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol 2011; 58:e44–e122.
48.
Marzilli M, Huqi A, Morrone D: Persistent angina: the Araba Phoenix of cardiology. Am J Cardiovasc Drugs 2010; 10(suppl 1): 27–32.
49.
Milo M, Nerla R, Tarzia P, Infusino F, Battipaglia I, Sestito A, Lanza GA, Crea F: Coronary microvascular dysfunction after elective percutaneous coronary intervention: correlation with exercise stress test results. Int J Cardiol 2013; 168: 121–125.
50.
Henderson RA, Pocock SJ, Clayton TC, et al: Seven-year outcome in the RITA-2 trial: coronary angioplasty versus medical therapy. J Am Coll Cardiol 2003; 42: 1161–1170.
51.
Alderman EL, Kip KE, Whitlow PL, et al: Native coronary disease progression exceeds failed revascularization as cause of angina after five years in the Bypass Angioplasty Revascularization Investigation (BARI). J Am Coll Cardiol 2004; 44: 766–774.
52.
Boden WE, O’Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, Knudtson M, Dada M, Casperson P, Harris CL, Chaitman BR, Shaw L, Gosselin G, Nawaz S, Title LM, Gau G, Blaustein AS, Booth DC, Bates ER, Spertus JA, Berman DS, Mancini GB, Weintraub WS: Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007; 356: 1503–1516.
53.
McGill HC Jr, McMahan CA, Zieske AW, et al: Association of coronary heart disease risk factors with microscopic qualities of coronary atherosclerosis in youth. Circulation 2000; 102: 374–379.
54.
Nicoli G, Scalone G, Crea F: Acute myocardial infarction with no obstructive coronary atherosclerosis: mechanism and management. Eur Heart J 2015; 36: 475–481.
55.
Tonino PA, De Bruyne B, Pijls NH, et al: Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009; 360: 213–224.
56.
Maseri A: Coronary artery spasm and thrombosis: Cardiovascular Clinics 14 No. 1. J R Soc Med 1985; 78: 178.
57.
Vermeltfoort IAC, Raijmakers PGHM, Riphagen II, et al: Definitions and incidence of cardiac syndrome X: review and analysis of clinical data. Clin Res Cardiol 2010; 99: 475–481.
58.
Lanza GA, Crea F: Primary coronary microvascular dysfunction: clinical presentation pathophysiology and management. Circulation 2010; 121: 2317–2325.
59.
Marinescu MA, Löffler AI, Ouellette M, Smith L, Kramer CM, Bourque JM: Coronary microvascular dysfunction, microvascular angina, and treatment strategies. JACC Cardiovasc Imaging 2015; 8: 210–220.
60.
Sedlak T, Izadnegahdar M, Humphries KH, Bairey Merz CN: Sex-specific factors in microvascular angina. Can J Cardiol 2014; 30: 747–755.
61.
Paul TK, Sivanesan K, Schulman-Marcus J: Sex differences in nonobstructive coronary artery disease: recent insights and substantial knowledge gaps. Trends Cardiovasc Med 2017; 27: 173–179.
62.
Jespersen L, Hvelplund A, Abildstrom SZ, Pedersen F, Galatius S, Madsen JK, Jorgensen E, Kelbaek H, Prescott E: Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J 2012; 33: 734–744.
63.
Tschope C, Van LS: New insights in (inter)cellular mechanisms by heart failure with preserved ejection fraction. Curr Heart Fail Rep 2014; 11: 436–444.
64.
Crea F, Bairey Merz CN, Beltrame JF, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Camici PG; Coronary Vasomotion Disorders International Study Group (COVADIS): The parallel tales of microvascular angina and heart failure with preserved ejection fraction: a paradigm shift. Eur Heart J 2017; 38: 473–477.
65.
Paulus WJ, Tschope C: A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 2013; 62: 263–271.
66.
Mohammed SF, Hussain S, Mirzoyev SA, Edwards WD, Maleszewski JJ, Redfield MM: Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction. Circulation 2015; 131: 550–559.
67.
Pries AR, Reglin B: Coronary microcirculatory pathophysiology: can we afford it to remain a black box? Eur Heart J 2017; 38: 478–488.
68.
Johnston N, Schenck-Gustafsson K, Lagerqvist B: Are we using cardiovascular medications and coronary angiography appropriately in men and women with chest pain? Eur Heart J 2011; 32: 1331–1336.
69.
Guarini G, Huqi A, Morrone D, Capozza P, Todiere G, Marzilli M: Pharmacological approaches to coronary microvascular dysfunction. Pharmacol Ther 2014; 144: 283–302.
70.
Crea F, Camici PG, Bairey Merz CN: Coronary microvascular dysfunction: an update. Eur Heart J 2014; 35: 1101–1111.
71.
Pries AR, Badimon L, Bugiardini R, Camici PG, Dorobantu M, Duncker DJ, Escaned J, Koller A, Piek JJ, de Wit C: Coronary vascular regulation, remodelling, and collateralization: mechanisms and clinical implications on behalf of the working group on coronary pathophysiology and microcirculation. Eur Heart J 2015; 36: 3134–3146.
72.
Heusch G, Baumgart D, Camici P, Chilian W, Gregorini L, Hess O, Indolfi C, Rimoldi O: Alpha-adrenergic coronary vasoconstriction and myocardial ischemia in humans. Circulation 2000; 101: 689–694.
73.
Egashira K, Inou T, Hirooka Y, Yamada A, Urabe Y, Takeshita A: Evidence of impaired endothelium-dependent coronary vasodilatation in patients with angina pectoris and normal coronary angiograms. N Engl J Med 1993; 328: 1659–1664.
74.
Camici PG, d’Amati G, Rimoldi O: Coronary microvascular dysfunction: mechanisms and functional assessment. Nat Rev Cardiol 2015; 12: 48–62.
75.
Duncker DJ, Bache RJ: Regulation of coronary blood flow during exercise. Physiol Rev 2008; 88: 1009–1086.
76.
Suzuki H, Takeyama Y, Koba S, Suwa Y, Katagiri T: Small vessel pathology and coronary hemodynamics in patients with microvascular angina. Int J Cardiol 1994; 43: 139–150.
77.
Reglin B, Pries AR: Metabolic control of microvascular networks: oxygen sensing and beyond. J Vasc Res 2014; 51: 376–392.
78.
Porro B, Eligini S, Veglia F, Lualdi A, Squellerio I, Fiorelli S, Giovannardi M, Chiorino E, Dalla CA, Crisci M, Werba JP, Tremoli E, Cavalca V: Nitric oxide synthetic pathway in patients with microvascular angina and its relations with oxidative stress. Oxid Med Cell Longev 2014; 2014: 726539.
79.
Borer JS, Swedberg K, Komajda M, Ford I, Tavazzi L, Böhm M, Depre C, Wu Y, Maya J, Dominjon F: Efficacy profile of ivabradine in patients with heart failure plus angina pectoris. Cardiology 2016; 136: 138–144.
80.
Opie LH, Sonnenblick EH, Frishman W, Thadani U: Beta Blockers: Drugs for the Heart. Philadelphia, WB Saunders, 1995, pp 1–27.
81.
Husted SE, Ohman EM: Pharmacological and emerging therapies in the treatment of chronic angina. Lancet 2015; 386: 691–701.
82.
Amosova E, Andrejev E, Zaderey I, Rudenko U, Ceconi C, Ferrari R: Efficacy of ivabradine in combination with beta-blocker versus uptitration of beta-blocker in patients with stable angina. Cardiovasc Drugs Ther 2011; 2015; 25: 531–537.
83.
DiFrancesco D, Camm JA: Heart rate lowering by specific and selective I(f) current inhibition with ivabradine: a new therapeutic perspective in cardiovascular disease. Drugs 2004; 64: 1757–1765.
84.
Borer JS, Heuzey JY: Characterization of the heart rate-lowering action of ivabradine, a selective I(f) current inhibitor. Am J Ther 2008; 15: 461–473.
85.
Tagliamonte E, Cirillo T, Rigo F, et al: Ivabradine and bisoprolol on Doppler-derived coronary flow velocity reserve in patients with stable coronary artery disease: beyond the heart rate. Adv Ther 2015; 32: 757–767.
86.
Gloekler S, Traupe T, Stoller M, et al: The effect of heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease. Heart 2014; 100: 160–166.
87.
Jedlickova L, Merkovska L, Jackova L, et al: Effect of ivabradine on endothelial function in patients with stable angina pectoris: assessment with the Endo-PAT 2000 device. Adv Ther 2015; 32: 962–970.
88.
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: 540–548.
89.
Fox K, Ford I, Steg PG, Tendera M, Ferrari R; BEAUTIFUL Investigators: Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet 2008; 372: 807–816.
90.
Fox K, Ford I, Steg PG, Tendera M, Robertson M, Ferrari R; BEAUTIFUL investigators: 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: 2337–2345.
91.
Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R: Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med 2014; 371: 1091–1099.
92.
Tardif JC, Ponikowski P, Kahan T, et al: Effect of verapamil on mortality and major events after acute myocardial infarction (the Danish Verapamil Infarction Trial II – DAVIT II). Am J Cardiol 1990; 66: 779–785.
93.
Frishman WH, Sica DA: Calcium channel blockers; in Frishman WH, Sonnenblick EH, Sica DA (eds): Cardiovascular Pharmacotherapeutics. New York, McGraw-Hill, 2003.
94.
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: 939–953.
95.
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: 1269–1273.
96.
Poole-Wilson PA, Lubsen J, Kirwan BA, van Dalen FJ, 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: 849–857.
97.
Johnston N, Schenck-Gustafsson K, Lagerqvist B: Are we using cardiovascular medications and coronary angiography appropriately in men and women with chest pain? Eur Heart J 2011; 32: 1331–1336.
98.
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: 1249–1256.
99.
O’Rourke ST: Nitro vasodilators: pharmacology and use in the treatment of myocardial ischemia. Am J Pharm Educ 2002; 66: 177–180.
100.
Munzel T, Daiber A, Gori T: Nitrate therapy: new aspects concerning molecular action and tolerance. Circulation 2011; 123: 2132–2144.
101.
Suryapranata H, Serruys PW, De Feyter PJ, Verdouw PD, Hugenholtz PG: Coronary vasodilatory action after a single dose of nicorandil. Am J Cardiol 1988; 61: 292–297.
102.
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: 61J–65J.
103.
The 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: 1269–1275.
104.
Kantor PF, Lucien A, Kozak R, Lopaschuk GD: The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res 2000; 86: 580–588.
105.
Fragasso G, Perseghin G, De CF, et al: Effects of metabolic modulation by trimetazidine on left ventricular function and phospho-creatine/adenosine triphosphate ratio in patients with heart failure. Eur Heart J 2006; 27: 942–948.
106.
Peng S, et al: The efficacy of trimetazidine on stable angina pectoris: a meta-analysis of randomized clinical trials. Int J Cardiol 2014; 177: 780–785.
107.
Ciapponi A, Pizarro R, Harrison J: Trimetazidine for stable angina. Cochrane Database Syst Rev 2017; 20:CD003614.
108.
Kim JS, Kim CH, Chun KJ, et al: Effects of trimetazidine in patients with acute myocardial infarction: data from the Korean Acute Myocardial Infarction Registry. Clin Res Cardiol 2013; 102: 915–922.
109.
Marazzi G, Wajngarten M, Vitale C, et al: Effect of free fatty acid inhibition on silent and symptomatic myocardial ischemia in diabetic patients with coronary artery disease. Int J Cardiol 2007; 120: 79–84.
110.
Gao D, Ning N, Niu X, Hao G, Meng Z: Trimetazidine: a meta-analysis of randomised controlled trials in heart failure. Heart 2011; 97: 278–286.
111.
Rayner E, Hartley, Sedlak T: Ranolazine: a contemporary review. J Am Heart Assoc 2016; 5:e003196.
112.
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: 953–959.e3.
113.
Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S, Wolff AA, Skene A, McCabe CH, Braunwald E; MERLIN-TIMI 36 Trial Investigators: 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: 1775–1783.
114.
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: 1504–1513.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.