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06.08.2016 | ORIGINAL ARTICLE

Pharmacological Agents Targeting Myocardial Metabolism for the Management of Chronic Stable Angina : an Update

verfasst von: Giacinta Guarini, Alda Huqi, Doralisa Morrone, Mario Marzilli

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 4/2016

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Abstract

Despite continuous advances in myocardial revascularization procedures and intracoronary devices, patients with ischemic heart disease (IHD) still experience worse prognosis and poor quality of life (QoL). Indeed, chronic stable angina (CSA) is a common disease with a large burden on healthcare costs. Traditionally, CSA is interpreted as episodes of reversible myocardial ischemia related to the presence of stable coronary artery plaque causing myocardial demand/supply mismatch when myocardial oxygen consumption increases. Accordingly, revascularization procedures are performed with the aim to remove the flow limiting stenosis, whereas traditional medical therapy (hemodynamic agents) aims at reducing myocardial oxygen demands. However, although effective, none of these treatment strategies or their combination is either able to confer symptomatic relief in all patients, nor to reduce mortality. Failure to significantly improve QoL and prognosis may be attributed at least in part to this “restrictive” understanding of IHD. Despite for many years myocardial metabolic derangement has been overlooked, recently it has gained increased attention with the development of new pharmacological agents (metabolic modulators) able to influence myocardial substrate selection and utilization thus improving cardiac efficiency. Shifting cardiac metabolism from free fatty acids (FA) towards glucose is a promising approach for the treatment of patients with stable angina, independently of the underling disease (macrovascular and/or microvascular disease). In this sense cardiac metabolic modulators open the way to a “revolutionary” understanding of ischemic heart disease and its common clinical manifestations, where myocardial ischemia is no longer considered as the mere oxygen and metabolites demand/supply unbalance, but as an energetic disorder. Keeping in mind such an alternative approach to the disease, development of new pharmacological agents directed toward multiple metabolic targets is mandatory.
Literatur
1.
Zurück zum Zitat Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, Bugiardini R, Crea F, Cuisset T, Di Mario C, Ferreira JR, Gersh BJ, Gitt AK, Hulot JS, Marx N, Opie LH, Pfisterer M, Prescott E, Ruschitzka F, Sabate M, Senior R, Taggart DP, van der Wall EE, Vrints CJ, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Knuuti J, Valgimigli M, Bueno H, Claeys MJ, Donner-Banzhoff N, Erol C, Frank H, Funck-Brentano C, Gaemperli O, Gonzalez-Juanatey JR, Hamilos M, Hasdai D, Husted S, James SK, Kervinen K, Kolh P, Kristensen SD, Lancellotti P, Maggioni AP, Piepoli MF, Pries AR, Romeo F, Ryden L, Simoons ML, Sirnes PA, Steg PG, Timmis A, Wijns W, Windecker S, Yildirir A, Zamorano JL. 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.PubMedCrossRef Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, Bugiardini R, Crea F, Cuisset T, Di Mario C, Ferreira JR, Gersh BJ, Gitt AK, Hulot JS, Marx N, Opie LH, Pfisterer M, Prescott E, Ruschitzka F, Sabate M, Senior R, Taggart DP, van der Wall EE, Vrints CJ, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Knuuti J, Valgimigli M, Bueno H, Claeys MJ, Donner-Banzhoff N, Erol C, Frank H, Funck-Brentano C, Gaemperli O, Gonzalez-Juanatey JR, Hamilos M, Hasdai D, Husted S, James SK, Kervinen K, Kolh P, Kristensen SD, Lancellotti P, Maggioni AP, Piepoli MF, Pries AR, Romeo F, Ryden L, Simoons ML, Sirnes PA, Steg PG, Timmis A, Wijns W, Windecker S, Yildirir A, Zamorano JL. 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.PubMedCrossRef
2.
Zurück zum Zitat Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2014;131:e29–322.PubMedCrossRef Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2014;131:e29–322.PubMedCrossRef
3.
Zurück zum Zitat Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB: Heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation 2013;127:e6-e245. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB: Heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation 2013;127:e6-e245.
4.
Zurück zum Zitat Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F, Daly C, De Backer G, Hjemdahl P, Lopez-Sendon J, Marco J, Morais J, Pepper J, Sechtem U, Simoons M, Thygesen K, Priori SG, Blanc JJ, Budaj A, Camm J, Dean V, Deckers J, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo J, Zamorano JL. 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;27:1341–81.PubMedCrossRef Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F, Daly C, De Backer G, Hjemdahl P, Lopez-Sendon J, Marco J, Morais J, Pepper J, Sechtem U, Simoons M, Thygesen K, Priori SG, Blanc JJ, Budaj A, Camm J, Dean V, Deckers J, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo J, Zamorano JL. 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;27:1341–81.PubMedCrossRef
5.
Zurück zum Zitat 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;356:1503–16.PubMedCrossRef 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;356:1503–16.PubMedCrossRef
6.
Zurück zum Zitat Five-year clinical and functional outcome comparing bypass surgery and angioplasty in patients with multivessel coronary disease. A multicenter randomized trial. Writing Group for the Bypass Angioplasty Revascularization Investigation (BARI) Investigators. JAMA 1997;277:715–721. Five-year clinical and functional outcome comparing bypass surgery and angioplasty in patients with multivessel coronary disease. A multicenter randomized trial. Writing Group for the Bypass Angioplasty Revascularization Investigation (BARI) Investigators. JAMA 1997;277:715–721.
7.
Zurück zum Zitat Marzilli M, Huqi A, Morrone D. Persistent angina: the araba phoenix of cardiology. Am J Cardiovasc Drugs. 2010;10(Suppl 1):27–32.PubMedCrossRef Marzilli M, Huqi A, Morrone D. Persistent angina: the araba phoenix of cardiology. Am J Cardiovasc Drugs. 2010;10(Suppl 1):27–32.PubMedCrossRef
8.
Zurück zum Zitat 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;60:951–6.PubMedCrossRef 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;60:951–6.PubMedCrossRef
9.
Zurück zum Zitat Pepine CJ, Douglas PS. Rethinking stable ischemic heart disease: is this the beginning of a new era? J Am Coll Cardiol. 2012;60:957–9.PubMedCrossRef Pepine CJ, Douglas PS. Rethinking stable ischemic heart disease: is this the beginning of a new era? J Am Coll Cardiol. 2012;60:957–9.PubMedCrossRef
10.
Zurück zum Zitat Fihn SD, Blankenship JC, Alexander KP, Bittl JA, Byrne JG, Fletcher BJ, Fonarow GC, Lange RA, Levine GN, Maddox TM, Naidu SS, Ohman EM, Smith PK. 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. Circulation. 2014;130:1749–67.PubMedCrossRef Fihn SD, Blankenship JC, Alexander KP, Bittl JA, Byrne JG, Fletcher BJ, Fonarow GC, Lange RA, Levine GN, Maddox TM, Naidu SS, Ohman EM, Smith PK. 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. Circulation. 2014;130:1749–67.PubMedCrossRef
11.
Zurück zum Zitat Marzilli M, Affinito S. Meeting the challenge of chronic ischaemic heart disease with trimetazidine. Coron Artery Dis. 2005;16(Suppl 1):S23–7.PubMedCrossRef Marzilli M, Affinito S. Meeting the challenge of chronic ischaemic heart disease with trimetazidine. Coron Artery Dis. 2005;16(Suppl 1):S23–7.PubMedCrossRef
12.
Zurück zum Zitat Guarini G, Huqi A, Morrone D, Capozza P, Todiere G, Marzilli M. Pharmacological approaches to coronary microvascular dysfunction. Pharmacol Ther. 2014;144:283–302.PubMedCrossRef Guarini G, Huqi A, Morrone D, Capozza P, Todiere G, Marzilli M. Pharmacological approaches to coronary microvascular dysfunction. Pharmacol Ther. 2014;144:283–302.PubMedCrossRef
13.
Zurück zum Zitat Guarini G, Huqi A, Capozza P, Morrone D, Donati F, Marzilli M. Therapy against ischemic injury. Curr Pharm Des. 2013;19:4597–621.PubMedCrossRef Guarini G, Huqi A, Capozza P, Morrone D, Donati F, Marzilli M. Therapy against ischemic injury. Curr Pharm Des. 2013;19:4597–621.PubMedCrossRef
14.
Zurück zum Zitat Wolff AA, Rotmensch HH, Stanley WC, Ferrari R. Metabolic approaches to the treatment of ischemic heart disease: the clinicians' perspective. Heart Fail Rev. 2002;7:187–203.PubMedCrossRef Wolff AA, Rotmensch HH, Stanley WC, Ferrari R. Metabolic approaches to the treatment of ischemic heart disease: the clinicians' perspective. Heart Fail Rev. 2002;7:187–203.PubMedCrossRef
15.
16.
Zurück zum Zitat Stanley WC, Sabbah HN. Metabolic therapy for ischemic heart disease: the rationale for inhibition of fatty acid oxidation. Heart Fail Rev. 2005;10:275–9.PubMedCrossRef Stanley WC, Sabbah HN. Metabolic therapy for ischemic heart disease: the rationale for inhibition of fatty acid oxidation. Heart Fail Rev. 2005;10:275–9.PubMedCrossRef
17.
Zurück zum Zitat Stanley WC, Lopaschuk GD, Hall JL, McCormack JG. Regulation of myocardial carbohydrate metabolism under normal and ischaemic conditions. Potential for pharmacological interventions. Cardiovasc Res. 1997;33:243–57.PubMedCrossRef Stanley WC, Lopaschuk GD, Hall JL, McCormack JG. Regulation of myocardial carbohydrate metabolism under normal and ischaemic conditions. Potential for pharmacological interventions. Cardiovasc Res. 1997;33:243–57.PubMedCrossRef
18.
Zurück zum Zitat Stanley WC, Recchia FA, Lopaschuk GD. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev. 2005;85:1093–129.PubMedCrossRef Stanley WC, Recchia FA, Lopaschuk GD. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev. 2005;85:1093–129.PubMedCrossRef
19.
Zurück zum Zitat Jaswal JS, Keung W, Wang W, Ussher JR, Lopaschuk GD. Targeting fatty acid and carbohydrate oxidation--a novel therapeutic intervention in the ischemic and failing heart. Biochim Biophys Acta. 1813;2011:1333–50. Jaswal JS, Keung W, Wang W, Ussher JR, Lopaschuk GD. Targeting fatty acid and carbohydrate oxidation--a novel therapeutic intervention in the ischemic and failing heart. Biochim Biophys Acta. 1813;2011:1333–50.
20.
Zurück zum Zitat Rupp H, Zarain-Herzberg A, Maisch B. The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure. Herz. 2002;27:621–36.PubMedCrossRef Rupp H, Zarain-Herzberg A, Maisch B. The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure. Herz. 2002;27:621–36.PubMedCrossRef
21.
Zurück zum Zitat Stanley WC. Partial fatty acid oxidation inhibitors for stable angina. Expert Opin Investig Drugs. 2002;11:615–29.PubMedCrossRef Stanley WC. Partial fatty acid oxidation inhibitors for stable angina. Expert Opin Investig Drugs. 2002;11:615–29.PubMedCrossRef
22.
Zurück zum Zitat Sugden MC, Holness MJ. Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs. Am J Physiol Endocrinol Metab. 2003;284:E855–62.PubMedCrossRef Sugden MC, Holness MJ. Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs. Am J Physiol Endocrinol Metab. 2003;284:E855–62.PubMedCrossRef
23.
Zurück zum Zitat Spriet LL, Heigenhauser GJ. Regulation of pyruvate dehydrogenase (PDH) activity in human skeletal muscle during exercise. Exerc Sport Sci Rev. 2002;30:91–5.PubMedCrossRef Spriet LL, Heigenhauser GJ. Regulation of pyruvate dehydrogenase (PDH) activity in human skeletal muscle during exercise. Exerc Sport Sci Rev. 2002;30:91–5.PubMedCrossRef
24.
Zurück zum Zitat McVeigh JJ, Lopaschuk GD. Dichloroacetate stimulation of glucose oxidation improves recovery of ischemic rat hearts. Am J Phys. 1990;259:H1079–85. McVeigh JJ, Lopaschuk GD. Dichloroacetate stimulation of glucose oxidation improves recovery of ischemic rat hearts. Am J Phys. 1990;259:H1079–85.
25.
Zurück zum Zitat Bergman G, Atkinson L, Metcalfe J, Jackson N, Jewitt DE. Beneficial effect of enhanced myocardial carbohydrate utilisation after oxfenicine (L-hydroxyphenylglycine) in angina pectoris. Eur Heart J. 1980;1:247–53.PubMedCrossRef Bergman G, Atkinson L, Metcalfe J, Jackson N, Jewitt DE. Beneficial effect of enhanced myocardial carbohydrate utilisation after oxfenicine (L-hydroxyphenylglycine) in angina pectoris. Eur Heart J. 1980;1:247–53.PubMedCrossRef
26.
Zurück zum Zitat Cole PL, Beamer AD, McGowan N, Cantillon CO, Benfell K, Kelly RA, Hartley LH, Smith TW, Antman EM. Efficacy and safety of perhexiline maleate in refractory angina. A double-blind placebo-controlled clinical trial of a novel antianginal agent. Circulation. 1990;81:1260–70.PubMedCrossRef Cole PL, Beamer AD, McGowan N, Cantillon CO, Benfell K, Kelly RA, Hartley LH, Smith TW, Antman EM. Efficacy and safety of perhexiline maleate in refractory angina. A double-blind placebo-controlled clinical trial of a novel antianginal agent. Circulation. 1990;81:1260–70.PubMedCrossRef
27.
Zurück zum Zitat Klassen GA, Zborowska-Sluis DT, Wright GJ. Effects of oral perhexiline on canine myocardial flow distribution. Can J Physiol Pharmacol. 1980;58:543–9.PubMedCrossRef Klassen GA, Zborowska-Sluis DT, Wright GJ. Effects of oral perhexiline on canine myocardial flow distribution. Can J Physiol Pharmacol. 1980;58:543–9.PubMedCrossRef
28.
Zurück zum Zitat Unger SA, Kennedy JA, McFadden-Lewis K, Minerds K, Murphy GA, Horowitz JD. Dissociation between metabolic and efficiency effects of perhexiline in normoxic rat myocardium. J Cardiovasc Pharmacol. 2005;46:849–55.PubMedCrossRef Unger SA, Kennedy JA, McFadden-Lewis K, Minerds K, Murphy GA, Horowitz JD. Dissociation between metabolic and efficiency effects of perhexiline in normoxic rat myocardium. J Cardiovasc Pharmacol. 2005;46:849–55.PubMedCrossRef
29.
Zurück zum Zitat Lee L, Campbell R, Scheuermann-Freestone M, Taylor R, Gunaruwan P, Williams L, Ashrafian H, Horowitz J, Fraser AG, Clarke K, Frenneaux M. Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment. Circulation. 2005;112:3280–8.PubMedCrossRef Lee L, Campbell R, Scheuermann-Freestone M, Taylor R, Gunaruwan P, Williams L, Ashrafian H, Horowitz J, Fraser AG, Clarke K, Frenneaux M. Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment. Circulation. 2005;112:3280–8.PubMedCrossRef
30.
Zurück zum Zitat Beadle RM, Williams LK, Kuehl M, Bowater S, Abozguia K, Leyva F, Yousef Z, Wagenmakers AJ, Thies F, Horowitz J, Frenneaux MP. Improvement in cardiac energetics by perhexiline in heart failure due to dilated cardiomyopathy. JACC Heart Fail. 2015;3:202–11.PubMedCrossRef Beadle RM, Williams LK, Kuehl M, Bowater S, Abozguia K, Leyva F, Yousef Z, Wagenmakers AJ, Thies F, Horowitz J, Frenneaux MP. Improvement in cardiac energetics by perhexiline in heart failure due to dilated cardiomyopathy. JACC Heart Fail. 2015;3:202–11.PubMedCrossRef
31.
Zurück zum Zitat Barclay ML, Sawyers SM, Begg EJ, Zhang M, Roberts RL, Kennedy MA, Elliott JM. Correlation of CYP2D6 genotype with perhexiline phenotypic metabolizer status. Pharmacogenetics. 2003;13:627–32.PubMedCrossRef Barclay ML, Sawyers SM, Begg EJ, Zhang M, Roberts RL, Kennedy MA, Elliott JM. Correlation of CYP2D6 genotype with perhexiline phenotypic metabolizer status. Pharmacogenetics. 2003;13:627–32.PubMedCrossRef
32.
Zurück zum Zitat Maarman G, Marais E, Lochner A, du Toit EF. Effect of chronic CPT-1 inhibition on myocardial ischemia-reperfusion injury (I/R) in a model of diet-induced obesity. Cardiovasc Drugs Ther. 2012;26:205–16.PubMedCrossRef Maarman G, Marais E, Lochner A, du Toit EF. Effect of chronic CPT-1 inhibition on myocardial ischemia-reperfusion injury (I/R) in a model of diet-induced obesity. Cardiovasc Drugs Ther. 2012;26:205–16.PubMedCrossRef
33.
Zurück zum Zitat Lionetti V, Linke A, Chandler MP, Young ME, Penn MS, Gupte S, d'Agostino C, Hintze TH, Stanley WC, Recchia FA. Carnitine palmitoyl transferase-I inhibition prevents ventricular remodeling and delays decompensation in pacing-induced heart failure. Cardiovasc Res. 2005;66:454–61.PubMedCrossRef Lionetti V, Linke A, Chandler MP, Young ME, Penn MS, Gupte S, d'Agostino C, Hintze TH, Stanley WC, Recchia FA. Carnitine palmitoyl transferase-I inhibition prevents ventricular remodeling and delays decompensation in pacing-induced heart failure. Cardiovasc Res. 2005;66:454–61.PubMedCrossRef
34.
Zurück zum Zitat Chandler MP, Chavez PN, McElfresh TA, Huang H, Harmon CS, Stanley WC. Partial inhibition of fatty acid oxidation increases regional contractile power and efficiency during demand-induced ischemia. Cardiovasc Res. 2003;59:143–51.PubMedCrossRef Chandler MP, Chavez PN, McElfresh TA, Huang H, Harmon CS, Stanley WC. Partial inhibition of fatty acid oxidation increases regional contractile power and efficiency during demand-induced ischemia. Cardiovasc Res. 2003;59:143–51.PubMedCrossRef
35.
Zurück zum Zitat Greaves P, Martin J, Michel MC, Mompon P. Cardiac hypertrophy in the dog and rat induced by oxfenicine, an agent which modifies muscle metabolism. Arch Toxicol Suppl. 1984;7:488–93.PubMedCrossRef Greaves P, Martin J, Michel MC, Mompon P. Cardiac hypertrophy in the dog and rat induced by oxfenicine, an agent which modifies muscle metabolism. Arch Toxicol Suppl. 1984;7:488–93.PubMedCrossRef
36.
Zurück zum Zitat Bachmann E, Weber E. Biochemical mechanisms of oxfenicine cardiotoxicity. Pharmacology. 1988;36:238–48.PubMedCrossRef Bachmann E, Weber E. Biochemical mechanisms of oxfenicine cardiotoxicity. Pharmacology. 1988;36:238–48.PubMedCrossRef
37.
Zurück zum Zitat Dyck JR, Cheng JF, Stanley WC, Barr R, Chandler MP, Brown S, Wallace D, Arrhenius T, Harmon C, Yang G, Nadzan AM, Lopaschuk GD. Malonyl coenzyme a decarboxylase inhibition protects the ischemic heart by inhibiting fatty acid oxidation and stimulating glucose oxidation. Circ Res. 2004;94:e78–84.PubMedCrossRef Dyck JR, Cheng JF, Stanley WC, Barr R, Chandler MP, Brown S, Wallace D, Arrhenius T, Harmon C, Yang G, Nadzan AM, Lopaschuk GD. Malonyl coenzyme a decarboxylase inhibition protects the ischemic heart by inhibiting fatty acid oxidation and stimulating glucose oxidation. Circ Res. 2004;94:e78–84.PubMedCrossRef
38.
Zurück zum Zitat McClellan KJ, Plosker GL. Trimetazidine. A review of its use in stable angina pectoris and other coronary conditions. Drugs. 1999;58:143–57.PubMedCrossRef McClellan KJ, Plosker GL. Trimetazidine. A review of its use in stable angina pectoris and other coronary conditions. Drugs. 1999;58:143–57.PubMedCrossRef
39.
Zurück zum Zitat Bucci M, Borra R, Nagren K, Parkka JP, Del Ry S, Maggio R, Tuunanen H, Viljanen T, Cabiati M, Rigazio S, Taittonen M, Pagotto U, Parkkola R, Opie LH, Nuutila P, Knuuti J, Iozzo P. Trimetazidine reduces endogenous free fatty acid oxidation and improves myocardial efficiency in obese humans. Cardiovasc Ther. 2012;30:333–41.PubMedCrossRef Bucci M, Borra R, Nagren K, Parkka JP, Del Ry S, Maggio R, Tuunanen H, Viljanen T, Cabiati M, Rigazio S, Taittonen M, Pagotto U, Parkkola R, Opie LH, Nuutila P, Knuuti J, Iozzo P. Trimetazidine reduces endogenous free fatty acid oxidation and improves myocardial efficiency in obese humans. Cardiovasc Ther. 2012;30:333–41.PubMedCrossRef
40.
Zurück zum Zitat Vaillant F, Tsibiribi P, Bricca G, Bui-Xuan B, Bescond-Jacquet A, Tabib A, Descotes J, Timour Q. Trimetazidine protective effect against ischemia-induced susceptibility to ventricular fibrillation in pigs. Cardiovasc Drugs Ther. 2008;22:29–36.PubMedCrossRef Vaillant F, Tsibiribi P, Bricca G, Bui-Xuan B, Bescond-Jacquet A, Tabib A, Descotes J, Timour Q. Trimetazidine protective effect against ischemia-induced susceptibility to ventricular fibrillation in pigs. Cardiovasc Drugs Ther. 2008;22:29–36.PubMedCrossRef
41.
Zurück zum Zitat 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;86:580–8.PubMedCrossRef 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;86:580–8.PubMedCrossRef
42.
Zurück zum Zitat Lopaschuk GD. Optimizing cardiac energy metabolism: how can fatty acid and carbohydrate metabolism be manipulated? Coron Artery Dis. 2001;12(Suppl 1):S8–11.PubMed Lopaschuk GD. Optimizing cardiac energy metabolism: how can fatty acid and carbohydrate metabolism be manipulated? Coron Artery Dis. 2001;12(Suppl 1):S8–11.PubMed
43.
Zurück zum Zitat Blardi P, de Lalla A, Volpi L, Auteri A, Di Perri T. Increase of adenosine plasma levels after oral trimetazidine: a pharmacological preconditioning? Pharmacol Res. 2002;45:69–72.PubMedCrossRef Blardi P, de Lalla A, Volpi L, Auteri A, Di Perri T. Increase of adenosine plasma levels after oral trimetazidine: a pharmacological preconditioning? Pharmacol Res. 2002;45:69–72.PubMedCrossRef
44.
Zurück zum Zitat Polonski L, Dec I, Wojnar R, Wilczek K. Trimetazidine limits the effects of myocardial ischaemia during percutaneous coronary angioplasty. Curr Med Res Opin. 2002;18:389–96.PubMedCrossRef Polonski L, Dec I, Wojnar R, Wilczek K. Trimetazidine limits the effects of myocardial ischaemia during percutaneous coronary angioplasty. Curr Med Res Opin. 2002;18:389–96.PubMedCrossRef
45.
Zurück zum Zitat Rebrova TY, Lasukova TV, Afanas'ev SA, Perchatkin VA, Maksimov IV, Markov VA. Cardioprotective effect of trimetazidine during thrombolytic therapy in patients with acute myocardial infarction. Bull Exp Biol Med. 2002;134:559–61.PubMedCrossRef Rebrova TY, Lasukova TV, Afanas'ev SA, Perchatkin VA, Maksimov IV, Markov VA. Cardioprotective effect of trimetazidine during thrombolytic therapy in patients with acute myocardial infarction. Bull Exp Biol Med. 2002;134:559–61.PubMedCrossRef
46.
Zurück zum Zitat Levy S. Value of the combination of trimetazidine (Vastarel 20 mg) with diltiazem (Tildiem 60 mg) in stable effort angina. A double-blind versus placebo multicenter study. Ann Cardiol Angeiol (Paris). 1995;44:203–12. Levy S. Value of the combination of trimetazidine (Vastarel 20 mg) with diltiazem (Tildiem 60 mg) in stable effort angina. A double-blind versus placebo multicenter study. Ann Cardiol Angeiol (Paris). 1995;44:203–12.
47.
Zurück zum Zitat Brochier M, Demange J, Ducloux G, Monpere C, Warin JF. [Value of the combination of trimetazidine and a calcium inhibitor in the treatment of chronic coronary insufficiency. Double-blind controlled study versus placebo]. Ann Cardiol Angeiol (Paris). 1986;35:49–56. Brochier M, Demange J, Ducloux G, Monpere C, Warin JF. [Value of the combination of trimetazidine and a calcium inhibitor in the treatment of chronic coronary insufficiency. Double-blind controlled study versus placebo]. Ann Cardiol Angeiol (Paris). 1986;35:49–56.
48.
Zurück zum Zitat Deroux A, Brochier M, Demange J, Ducloux G, Monpere C. Warin JF: [therapeutic value of a combination of trimetazidine with a calcium inhibitor in the treatment of chronic coronary insufficiency]. Presse Med. 1986;15:1783–7.PubMed Deroux A, Brochier M, Demange J, Ducloux G, Monpere C. Warin JF: [therapeutic value of a combination of trimetazidine with a calcium inhibitor in the treatment of chronic coronary insufficiency]. Presse Med. 1986;15:1783–7.PubMed
49.
Zurück zum Zitat Gallet M. Clinical effectiveness of trimetazidine in stable effort angina. A double-blind versus placebo controlled study. Presse Med. 1986;15:1779–82.PubMed Gallet M. Clinical effectiveness of trimetazidine in stable effort angina. A double-blind versus placebo controlled study. Presse Med. 1986;15:1779–82.PubMed
50.
51.
Zurück zum Zitat Lu C, Dabrowski P, Fragasso G, Chierchia SL. Effects of trimetazidine on ischemic left ventricular dysfunction in patients with coronary artery disease. Am J Cardiol. 1998;82:898–901.PubMedCrossRef Lu C, Dabrowski P, Fragasso G, Chierchia SL. Effects of trimetazidine on ischemic left ventricular dysfunction in patients with coronary artery disease. Am J Cardiol. 1998;82:898–901.PubMedCrossRef
52.
Zurück zum Zitat Bricaud H, Brottier L, Barat JL, Combe C, Boussens B, Bonnet J. Cardioprotective effect of trimetazidine in severe ischemic cardiomyopathy. Cardiovasc Drugs Ther. 1990;4(Suppl 4):861–5.PubMedCrossRef Bricaud H, Brottier L, Barat JL, Combe C, Boussens B, Bonnet J. Cardioprotective effect of trimetazidine in severe ischemic cardiomyopathy. Cardiovasc Drugs Ther. 1990;4(Suppl 4):861–5.PubMedCrossRef
53.
Zurück zum Zitat Szwed H, Hradec J, Preda I. Anti-ischaemic efficacy and tolerability of trimetazidine administered to patients with angina pectoris: results of three studies. Coron Artery Dis. 2001;12(Suppl 1):S25–8.PubMed Szwed H, Hradec J, Preda I. Anti-ischaemic efficacy and tolerability of trimetazidine administered to patients with angina pectoris: results of three studies. Coron Artery Dis. 2001;12(Suppl 1):S25–8.PubMed
54.
Zurück zum Zitat Passeron J. Effectiveness of trimetazidine in stable effort angina due to chronic coronary insufficiency. A double-blind versus placebo study. Presse Med. 1986;15:1775–8.PubMed Passeron J. Effectiveness of trimetazidine in stable effort angina due to chronic coronary insufficiency. A double-blind versus placebo study. Presse Med. 1986;15:1775–8.PubMed
55.
Zurück zum Zitat Hanania G, Haiat R, Olive T, Maalouf B, Michel D, Martelet M, Godard S. [Coronary artery disease observed in general hospitals: ETTIC study. Comparison between trimetazidine and mononitrate isosorbide for patients receiving betablockers]. Ann Cardiol Angeiol (Paris). 2002;51:268–74.CrossRef Hanania G, Haiat R, Olive T, Maalouf B, Michel D, Martelet M, Godard S. [Coronary artery disease observed in general hospitals: ETTIC study. Comparison between trimetazidine and mononitrate isosorbide for patients receiving betablockers]. Ann Cardiol Angeiol (Paris). 2002;51:268–74.CrossRef
56.
Zurück zum Zitat Szwed H, Sadowski Z, Elikowski W, Koronkiewicz A, Mamcarz A, Orszulak W, Skibinska E, Szymczak K, Swiatek J, Winter M. 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;22:2267–74.PubMedCrossRef Szwed H, Sadowski Z, Elikowski W, Koronkiewicz A, Mamcarz A, Orszulak W, Skibinska E, Szymczak K, Swiatek J, Winter M. 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;22:2267–74.PubMedCrossRef
57.
Zurück zum Zitat Szwed H. Clinical benefits of trimetazidine in patients with recurrent angina. Coron Artery Dis. 2004;15(Suppl 1):S17–21.PubMed Szwed H. Clinical benefits of trimetazidine in patients with recurrent angina. Coron Artery Dis. 2004;15(Suppl 1):S17–21.PubMed
58.
Zurück zum Zitat Chazov EI, Lepakchin VK, Zharova EA, Fitilev SB, Levin AM, Rumiantzeva EG, Fitileva TB. Trimetazidine in angina combination therapy--the TACT study: trimetazidine versus conventional treatment in patients with stable angina pectoris in a randomized, placebo-controlled, multicenter study. Am J Ther. 2005;12:35–42.PubMedCrossRef Chazov EI, Lepakchin VK, Zharova EA, Fitilev SB, Levin AM, Rumiantzeva EG, Fitileva TB. Trimetazidine in angina combination therapy--the TACT study: trimetazidine versus conventional treatment in patients with stable angina pectoris in a randomized, placebo-controlled, multicenter study. Am J Ther. 2005;12:35–42.PubMedCrossRef
59.
Zurück zum Zitat Michaelides A, Spiropoulos K, Dimopoulos K, Athanasiades D, Toutouzas P. Antianginal efficacy of the combination of trimetazidine-propranolol compared with isosorbide dinitrate-propranolol in patients with stable angina. Clinical Drug Investigation. 1997;13:8–14.CrossRef Michaelides A, Spiropoulos K, Dimopoulos K, Athanasiades D, Toutouzas P. Antianginal efficacy of the combination of trimetazidine-propranolol compared with isosorbide dinitrate-propranolol in patients with stable angina. Clinical Drug Investigation. 1997;13:8–14.CrossRef
60.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
61.
Zurück zum Zitat Grabczewska Z, Bialoszynski T, Szymanski P, Sukiennik A, Swiatkiewicz I, Kozinski M, Kochman W, Grzesk G, Kubica J. The effect of trimetazidine added to maximal anti-ischemic therapy in patients with advanced coronary artery disease. Cardiol J. 2008;15:344–50.PubMed Grabczewska Z, Bialoszynski T, Szymanski P, Sukiennik A, Swiatkiewicz I, Kozinski M, Kochman W, Grzesk G, Kubica J. The effect of trimetazidine added to maximal anti-ischemic therapy in patients with advanced coronary artery disease. Cardiol J. 2008;15:344–50.PubMed
62.
Zurück zum Zitat Marazzi G, Wajngarten M, Vitale C, Patrizi R, Pelliccia F, Gebara O, Pierri H, Ramires JA, Volterrani M, Fini M, Rosano GM. 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.PubMedCrossRef Marazzi G, Wajngarten M, Vitale C, Patrizi R, Pelliccia F, Gebara O, Pierri H, Ramires JA, Volterrani M, Fini M, Rosano GM. 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.PubMedCrossRef
63.
Zurück zum Zitat 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;177:780–5.PubMedCrossRef 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;177:780–5.PubMedCrossRef
64.
Zurück zum Zitat Marzilli M. Cardioprotective effects of trimetazidine: a review. Curr Med Res Opin. 2003;19:661–72.PubMedCrossRef Marzilli M. Cardioprotective effects of trimetazidine: a review. Curr Med Res Opin. 2003;19:661–72.PubMedCrossRef
65.
Zurück zum Zitat Danchin N, Marzilli M, Parkhomenko A, Ribeiro JP. Efficacy comparison of trimetazidine with therapeutic alternatives in stable angina pectoris: a network meta-analysis. Cardiology. 2011;120:59–72.PubMedCrossRef Danchin N, Marzilli M, Parkhomenko A, Ribeiro JP. Efficacy comparison of trimetazidine with therapeutic alternatives in stable angina pectoris: a network meta-analysis. Cardiology. 2011;120:59–72.PubMedCrossRef
66.
Zurück zum Zitat Marzilli M. Does trimetazidine prevent myocardial injury after percutaneous coronary intervention? Nat Clin Pract Cardiovasc Med. 2008;5:16–7.PubMedCrossRef Marzilli M. Does trimetazidine prevent myocardial injury after percutaneous coronary intervention? Nat Clin Pract Cardiovasc Med. 2008;5:16–7.PubMedCrossRef
67.
Zurück zum Zitat Danchin N. Clinical benefits of a metabolic approach with trimetazidine in revascularized patients with angina. Am J Cardiol. 2006;98:8J–13J.PubMedCrossRef Danchin N. Clinical benefits of a metabolic approach with trimetazidine in revascularized patients with angina. Am J Cardiol. 2006;98:8J–13J.PubMedCrossRef
68.
Zurück zum Zitat Vasiuk Iu A, Shal'nova SA, Shkol'nik EL, Kulikov KG. [The (PRIMA) Study. Comparison of clinical effect of trimetazidine MR in men and women]. Kardiologiia. 2011;51:11–5.PubMed Vasiuk Iu A, Shal'nova SA, Shkol'nik EL, Kulikov KG. [The (PRIMA) Study. Comparison of clinical effect of trimetazidine MR in men and women]. Kardiologiia. 2011;51:11–5.PubMed
69.
Zurück zum Zitat Rodriguez Padial L, Maicas Bellido C, Velazquez Martin M, Gil Polo B. A prospective study on trimetazidine effectiveness and tolerability in diabetic patients in association to the previous treatment of their coronary disease. DIETRIC study. Rev Clin Esp. 2005;205:57–62.PubMedCrossRef Rodriguez Padial L, Maicas Bellido C, Velazquez Martin M, Gil Polo B. A prospective study on trimetazidine effectiveness and tolerability in diabetic patients in association to the previous treatment of their coronary disease. DIETRIC study. Rev Clin Esp. 2005;205:57–62.PubMedCrossRef
70.
Zurück zum Zitat Ribeiro LW, Ribeiro JP, Stein R, Leitao C, Polanczyk CA. Trimetazidine added to combined hemodynamic antianginal therapy in patients with type 2 diabetes: a randomized crossover trial. Am Heart J. 2007;154(78):e71–7. Ribeiro LW, Ribeiro JP, Stein R, Leitao C, Polanczyk CA. Trimetazidine added to combined hemodynamic antianginal therapy in patients with type 2 diabetes: a randomized crossover trial. Am Heart J. 2007;154(78):e71–7.
71.
Zurück zum Zitat Sellier P, Audouin P, Payen B, Corona P, Duong TC, Ourbak P. Acute effects of trimetazidine evaluated by exercise testing. Eur J Clin Pharmacol. 1987;33:205–7.PubMedCrossRef Sellier P, Audouin P, Payen B, Corona P, Duong TC, Ourbak P. Acute effects of trimetazidine evaluated by exercise testing. Eur J Clin Pharmacol. 1987;33:205–7.PubMedCrossRef
72.
Zurück zum Zitat Fragasso G, Palloshi A, Puccetti P, Silipigni C, Rossodivita A, Pala M, Calori G, Alfieri O, Margonato A. A randomized clinical trial of trimetazidine, a partial free fatty acid oxidation inhibitor, in patients with heart failure. J Am Coll Cardiol. 2006;48:992–8.PubMedCrossRef Fragasso G, Palloshi A, Puccetti P, Silipigni C, Rossodivita A, Pala M, Calori G, Alfieri O, Margonato A. A randomized clinical trial of trimetazidine, a partial free fatty acid oxidation inhibitor, in patients with heart failure. J Am Coll Cardiol. 2006;48:992–8.PubMedCrossRef
73.
Zurück zum Zitat Zhao P, Zhang J, Yin XG, Maharaj P, Narraindoo S, Cui LQ, Tang YS. The effect of trimetazidine on cardiac function in diabetic patients with idiopathic dilated cardiomyopathy. Life Sci. 2013;92:633–8.PubMedCrossRef Zhao P, Zhang J, Yin XG, Maharaj P, Narraindoo S, Cui LQ, Tang YS. The effect of trimetazidine on cardiac function in diabetic patients with idiopathic dilated cardiomyopathy. Life Sci. 2013;92:633–8.PubMedCrossRef
74.
Zurück zum Zitat Hu B, Li W, Xu T, Chen T, Guo J. Evaluation of trimetazidine in angina pectoris by echocardiography and radionuclide angiography: a meta-analysis of randomized, controlled trials. Clin Cardiol. 2011;34:395–400.PubMedCrossRef Hu B, Li W, Xu T, Chen T, Guo J. Evaluation of trimetazidine in angina pectoris by echocardiography and radionuclide angiography: a meta-analysis of randomized, controlled trials. Clin Cardiol. 2011;34:395–400.PubMedCrossRef
75.
Zurück zum Zitat Fragasso G, Piatti Md PM, Monti L, Palloshi A, Setola E, Puccetti P, Calori G, Lopaschuk GD, Margonato A. Short- and long-term beneficial effects of trimetazidine in patients with diabetes and ischemic cardiomyopathy. Am Heart J. 2003;146:E18.PubMedCrossRef Fragasso G, Piatti Md PM, Monti L, Palloshi A, Setola E, Puccetti P, Calori G, Lopaschuk GD, Margonato A. Short- and long-term beneficial effects of trimetazidine in patients with diabetes and ischemic cardiomyopathy. Am Heart J. 2003;146:E18.PubMedCrossRef
76.
Zurück zum Zitat Fragasso G, Rosano G, Baek SH, Sisakian H, Di Napoli P, Alberti L, Calori G, Kang SM, Sahakyan L, Sanosyan A, Vitale C, Marazzi G, Margonato A, Belardinelli R. Effect of partial fatty acid oxidation inhibition with trimetazidine on mortality and morbidity in heart failure: results from an international multicentre retrospective cohort study. Int J Cardiol. 2013;163:320–5.PubMedCrossRef Fragasso G, Rosano G, Baek SH, Sisakian H, Di Napoli P, Alberti L, Calori G, Kang SM, Sahakyan L, Sanosyan A, Vitale C, Marazzi G, Margonato A, Belardinelli R. Effect of partial fatty acid oxidation inhibition with trimetazidine on mortality and morbidity in heart failure: results from an international multicentre retrospective cohort study. Int J Cardiol. 2013;163:320–5.PubMedCrossRef
77.
Zurück zum Zitat Rosano GM, Vitale C, Sposato B, Mercuro G, Fini M. Trimetazidine improves left ventricular function in diabetic patients with coronary artery disease: a double-blind placebo-controlled study. Cardiovasc Diabetol. 2003;2:16.PubMedPubMedCentralCrossRef Rosano GM, Vitale C, Sposato B, Mercuro G, Fini M. Trimetazidine improves left ventricular function in diabetic patients with coronary artery disease: a double-blind placebo-controlled study. Cardiovasc Diabetol. 2003;2:16.PubMedPubMedCentralCrossRef
78.
Zurück zum Zitat Monti LD, Setola E, Fragasso G, Camisasca RP, Lucotti P, Galluccio E, Origgi A, Margonato A, Piatti P. Metabolic and endothelial effects of trimetazidine on forearm skeletal muscle in patients with type 2 diabetes and ischemic cardiomyopathy. Am J Physiol Endocrinol Metab. 2006;290:E54–9.PubMedCrossRef Monti LD, Setola E, Fragasso G, Camisasca RP, Lucotti P, Galluccio E, Origgi A, Margonato A, Piatti P. Metabolic and endothelial effects of trimetazidine on forearm skeletal muscle in patients with type 2 diabetes and ischemic cardiomyopathy. Am J Physiol Endocrinol Metab. 2006;290:E54–9.PubMedCrossRef
79.
Zurück zum Zitat Gunes Y, Guntekin U, Tuncer M, Sahin M. Improved left and right ventricular functions with trimetazidine in patients with heart failure: a tissue Doppler study. Heart Vessel. 2009;24:277–82.CrossRef Gunes Y, Guntekin U, Tuncer M, Sahin M. Improved left and right ventricular functions with trimetazidine in patients with heart failure: a tissue Doppler study. Heart Vessel. 2009;24:277–82.CrossRef
80.
Zurück zum Zitat Marazzi G, Gebara O, Vitale C, Caminiti G, Wajngarten M, Volterrani M, Ramires JA, Rosano G, Fini M. Effect of trimetazidine on quality of life in elderly patients with ischemic dilated cardiomyopathy. Adv Ther. 2009;26:455–61.PubMedCrossRef Marazzi G, Gebara O, Vitale C, Caminiti G, Wajngarten M, Volterrani M, Ramires JA, Rosano G, Fini M. Effect of trimetazidine on quality of life in elderly patients with ischemic dilated cardiomyopathy. Adv Ther. 2009;26:455–61.PubMedCrossRef
81.
Zurück zum Zitat Belardinelli R, Lacalaprice F, Faccenda E, Volpe L. Trimetazidine potentiates the effects of exercise training in patients with ischemic cardiomyopathy referred for cardiac rehabilitation. Eur J Cardiovasc Prev Rehabil. 2008;15:533–40.PubMedCrossRef Belardinelli R, Lacalaprice F, Faccenda E, Volpe L. Trimetazidine potentiates the effects of exercise training in patients with ischemic cardiomyopathy referred for cardiac rehabilitation. Eur J Cardiovasc Prev Rehabil. 2008;15:533–40.PubMedCrossRef
82.
Zurück zum Zitat Gao D, Ning N, Niu X, Hao G, Meng Z. Trimetazidine: a meta-analysis of randomised controlled trials in heart failure. Heart. 2011;97:278–86.PubMedCrossRef Gao D, Ning N, Niu X, Hao G, Meng Z. Trimetazidine: a meta-analysis of randomised controlled trials in heart failure. Heart. 2011;97:278–86.PubMedCrossRef
83.
Zurück zum Zitat El-Kady T, El-Sabban K, Gabaly M, Sabry A, Abdel-Hady S. Effects of trimetazidine on myocardial perfusion and the contractile response of chronically dysfunctional myocardium in ischemic cardiomyopathy: a 24-month study. Am J Cardiovasc Drugs. 2005;5:271–8.PubMedCrossRef El-Kady T, El-Sabban K, Gabaly M, Sabry A, Abdel-Hady S. Effects of trimetazidine on myocardial perfusion and the contractile response of chronically dysfunctional myocardium in ischemic cardiomyopathy: a 24-month study. Am J Cardiovasc Drugs. 2005;5:271–8.PubMedCrossRef
84.
Zurück zum Zitat Tritto I, Wang P, Kuppusamy P, Giraldez R, Zweier JL, Ambrosio G. The anti-anginal drug trimetazidine reduces neutrophil-mediated cardiac reperfusion injury. J Cardiovasc Pharmacol. 2005;46:89–98.PubMedCrossRef Tritto I, Wang P, Kuppusamy P, Giraldez R, Zweier JL, Ambrosio G. The anti-anginal drug trimetazidine reduces neutrophil-mediated cardiac reperfusion injury. J Cardiovasc Pharmacol. 2005;46:89–98.PubMedCrossRef
85.
Zurück zum Zitat Williams FM, Tanda K, Kus M, Williams TJ. Trimetazidine inhibits neutrophil accumulation after myocardial ischaemia and reperfusion in rabbits. J Cardiovasc Pharmacol. 1993;22:828–33.PubMedCrossRef Williams FM, Tanda K, Kus M, Williams TJ. Trimetazidine inhibits neutrophil accumulation after myocardial ischaemia and reperfusion in rabbits. J Cardiovasc Pharmacol. 1993;22:828–33.PubMedCrossRef
86.
Zurück zum Zitat Khan M, Meduru S, Mostafa M, Khan S, Hideg K, Kuppusamy P. Trimetazidine, administered at the onset of reperfusion, ameliorates myocardial dysfunction and injury by activation of p38 mitogen-activated protein kinase and Akt signaling. J Pharmacol Exp Ther. 2010;333:421–9.PubMedPubMedCentralCrossRef Khan M, Meduru S, Mostafa M, Khan S, Hideg K, Kuppusamy P. Trimetazidine, administered at the onset of reperfusion, ameliorates myocardial dysfunction and injury by activation of p38 mitogen-activated protein kinase and Akt signaling. J Pharmacol Exp Ther. 2010;333:421–9.PubMedPubMedCentralCrossRef
87.
Zurück zum Zitat Bonello L, Sbragia P, Amabile N, Com O, Pierre SV, Levy S, Paganelli F. Protective effect of an acute oral loading dose of trimetazidine on myocardial injury following percutaneous coronary intervention. Heart. 2007;93:703–7.PubMedPubMedCentralCrossRef Bonello L, Sbragia P, Amabile N, Com O, Pierre SV, Levy S, Paganelli F. Protective effect of an acute oral loading dose of trimetazidine on myocardial injury following percutaneous coronary intervention. Heart. 2007;93:703–7.PubMedPubMedCentralCrossRef
88.
Zurück zum Zitat Fabiani JN, Ponzio O, Emerit I, Massonet-Castel S, Paris M, Chevalier P, Jebara V, Carpentier A. Cardioprotective effect of trimetazidine during coronary artery graft surgery. J Cardiovasc Surg. 1992;33:486–91. Fabiani JN, Ponzio O, Emerit I, Massonet-Castel S, Paris M, Chevalier P, Jebara V, Carpentier A. Cardioprotective effect of trimetazidine during coronary artery graft surgery. J Cardiovasc Surg. 1992;33:486–91.
89.
Zurück zum Zitat Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J, Wang W, Skettino SL, Wolff AA. 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;291:309–16.PubMedCrossRef Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J, Wang W, Skettino SL, Wolff AA. 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;291:309–16.PubMedCrossRef
90.
Zurück zum Zitat Rousseau MF, Pouleur H, Cocco G, Wolff AA. Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris. Am J Cardiol. 2005;95:311–6.PubMedCrossRef Rousseau MF, Pouleur H, Cocco G, Wolff AA. Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris. Am J Cardiol. 2005;95:311–6.PubMedCrossRef
91.
Zurück zum Zitat Chaitman BR, Skettino SL, Parker JO, Hanley P, Meluzin J, Kuch J, Pepine CJ, Wang W, Nelson JJ, Hebert DA, Wolff AA. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol. 2004;43:1375–82.PubMedCrossRef Chaitman BR, Skettino SL, Parker JO, Hanley P, Meluzin J, Kuch J, Pepine CJ, Wang W, Nelson JJ, Hebert DA, Wolff AA. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol. 2004;43:1375–82.PubMedCrossRef
92.
Zurück zum Zitat Zhang XQ, Yamada S, Barry WH. Ranolazine inhibits an oxidative stress-induced increase in myocyte sodium and calcium loading during simulated-demand ischemia. J Cardiovasc Pharmacol. 2008;51:443–9.PubMedCrossRef Zhang XQ, Yamada S, Barry WH. Ranolazine inhibits an oxidative stress-induced increase in myocyte sodium and calcium loading during simulated-demand ischemia. J Cardiovasc Pharmacol. 2008;51:443–9.PubMedCrossRef
93.
Zurück zum Zitat Maier LS. A novel mechanism for the treatment of angina, arrhythmias, and diastolic dysfunction: inhibition of late I(Na) using ranolazine. J Cardiovasc Pharmacol. 2009;54:279–86.PubMedCrossRef Maier LS. A novel mechanism for the treatment of angina, arrhythmias, and diastolic dysfunction: inhibition of late I(Na) using ranolazine. J Cardiovasc Pharmacol. 2009;54:279–86.PubMedCrossRef
94.
Zurück zum Zitat Jerling M. Clinical Pharmacokinetics of ranolazine Clin Pharmacokinetic. 2006;45:469–91. Jerling M. Clinical Pharmacokinetics of ranolazine Clin Pharmacokinetic. 2006;45:469–91.
95.
Zurück zum Zitat Kaliebe JW, Murdock DK. Suppression of non-sustained ventricular tachycardia with ranolazine: a case report. Wmj. 2009;108:373–5.PubMed Kaliebe JW, Murdock DK. Suppression of non-sustained ventricular tachycardia with ranolazine: a case report. Wmj. 2009;108:373–5.PubMed
96.
Zurück zum Zitat Belardinelli L, Liu G, Smith-Maxwell C, Wang WQ, El-Bizri N, Hirakawa R, Karpinski S, Li CH, Hu L, Li XJ, Crumb W, Wu L, Koltun D, Zablocki J, Yao L, Dhalla AK, Rajamani S, Shryock JC. A novel, potent, and selective inhibitor of cardiac late sodium current suppresses experimental arrhythmias. J Pharmacol Exp Ther. 2013;344:23–32.PubMedCrossRef Belardinelli L, Liu G, Smith-Maxwell C, Wang WQ, El-Bizri N, Hirakawa R, Karpinski S, Li CH, Hu L, Li XJ, Crumb W, Wu L, Koltun D, Zablocki J, Yao L, Dhalla AK, Rajamani S, Shryock JC. A novel, potent, and selective inhibitor of cardiac late sodium current suppresses experimental arrhythmias. J Pharmacol Exp Ther. 2013;344:23–32.PubMedCrossRef
97.
Zurück zum Zitat Belardinelli L, Shryock JC, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine. Heart. 2006;92(Suppl 4):iv6–iv14.PubMedPubMedCentral Belardinelli L, Shryock JC, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine. Heart. 2006;92(Suppl 4):iv6–iv14.PubMedPubMedCentral
98.
Zurück zum Zitat Antoons G, Oros A, Beekman JD, Engelen MA, Houtman MJ, Belardinelli L, Stengl M, Vos MA. Late na(+) current inhibition by ranolazine reduces torsades de pointes in the chronic atrioventricular block dog model. J Am Coll Cardiol. 2010;55:801–9.PubMedCrossRef Antoons G, Oros A, Beekman JD, Engelen MA, Houtman MJ, Belardinelli L, Stengl M, Vos MA. Late na(+) current inhibition by ranolazine reduces torsades de pointes in the chronic atrioventricular block dog model. J Am Coll Cardiol. 2010;55:801–9.PubMedCrossRef
99.
Zurück zum Zitat Aidonidis I, Doulas K, Hatziefthimiou A, Tagarakis G, Simopoulos V, Rizos I, Tsilimingas N, Molyvdas PA. Ranolazine-induced postrepolarization refractoriness suppresses induction of atrial flutter and fibrillation in anesthetized rabbits. J Cardiovasc Pharmacol Ther. 2013;18:94–101.PubMedCrossRef Aidonidis I, Doulas K, Hatziefthimiou A, Tagarakis G, Simopoulos V, Rizos I, Tsilimingas N, Molyvdas PA. Ranolazine-induced postrepolarization refractoriness suppresses induction of atrial flutter and fibrillation in anesthetized rabbits. J Cardiovasc Pharmacol Ther. 2013;18:94–101.PubMedCrossRef
100.
Zurück zum Zitat Coppini R, Ferrantini C, Yao L, Fan P, Del Lungo M, Stillitano F, Sartiani L, Tosi B, Suffredini S, Tesi C, Yacoub M, Olivotto I, Belardinelli L, Poggesi C, Cerbai E, Mugelli A. Late sodium current inhibition reverses electromechanical dysfunction in human hypertrophic cardiomyopathy. Circulation. 2013;127:575–84.PubMedCrossRef Coppini R, Ferrantini C, Yao L, Fan P, Del Lungo M, Stillitano F, Sartiani L, Tosi B, Suffredini S, Tesi C, Yacoub M, Olivotto I, Belardinelli L, Poggesi C, Cerbai E, Mugelli A. Late sodium current inhibition reverses electromechanical dysfunction in human hypertrophic cardiomyopathy. Circulation. 2013;127:575–84.PubMedCrossRef
101.
Zurück zum Zitat Burashnikov A, Antzelevitch C. Role of late sodium channel current block in the management of atrial fibrillation. Cardiovasc Drugs Ther. 2013;27:79–89.PubMedPubMedCentralCrossRef Burashnikov A, Antzelevitch C. Role of late sodium channel current block in the management of atrial fibrillation. Cardiovasc Drugs Ther. 2013;27:79–89.PubMedPubMedCentralCrossRef
102.
Zurück zum Zitat Pelliccia F, Pasceri V, Marazzi G, Rosano G, Greco C, Gaudio C. A pilot randomized study of ranolazine for reduction of myocardial damage during elective percutaneous coronary intervention. Am Heart J. 2012;163:1019–23.PubMedCrossRef Pelliccia F, Pasceri V, Marazzi G, Rosano G, Greco C, Gaudio C. A pilot randomized study of ranolazine for reduction of myocardial damage during elective percutaneous coronary intervention. Am Heart J. 2012;163:1019–23.PubMedCrossRef
103.
Zurück zum Zitat Mehta PK, Goykhman P, Thomson LE, Shufelt C, Wei J, Yang Y, Gill E, Minissian M, Shaw LJ, Slomka PJ, Slivka M, Berman DS, Bairey Merz CN. Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. JACC Cardiovasc Imaging. 2011;4:514–22.PubMedCrossRef Mehta PK, Goykhman P, Thomson LE, Shufelt C, Wei J, Yang Y, Gill E, Minissian M, Shaw LJ, Slomka PJ, Slivka M, Berman DS, Bairey Merz CN. Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. JACC Cardiovasc Imaging. 2011;4:514–22.PubMedCrossRef
104.
Zurück zum Zitat Stone PH, Chaitman BR, Stocke K, Sano J, DeVault A, Koch GG. The anti-ischemic mechanism of action of ranolazine in stable ischemic heart disease. J Am Coll Cardiol. 2010;56:934–42.PubMedCrossRef Stone PH, Chaitman BR, Stocke K, Sano J, DeVault A, Koch GG. The anti-ischemic mechanism of action of ranolazine in stable ischemic heart disease. J Am Coll Cardiol. 2010;56:934–42.PubMedCrossRef
105.
Zurück zum Zitat Chandler MP, Stanley WC, Morita H, Suzuki G, Roth BA, Blackburn B, Wolff A, Sabbah HN. Short-term treatment with ranolazine improves mechanical efficiency in dogs with chronic heart failure. Circ Res. 2002;91:278–80.PubMedCrossRef Chandler MP, Stanley WC, Morita H, Suzuki G, Roth BA, Blackburn B, Wolff A, Sabbah HN. Short-term treatment with ranolazine improves mechanical efficiency in dogs with chronic heart failure. Circ Res. 2002;91:278–80.PubMedCrossRef
106.
Zurück zum Zitat Rastogi S, Sharov VG, Mishra S, Gupta RC, Blackburn B, Belardinelli L, Stanley WC, Sabbah HN. Ranolazine combined with enalapril or metoprolol prevents progressive LV dysfunction and remodeling in dogs with moderate heart failure. Am J Physiol Heart Circ Physiol. 2008;295:H2149–55.PubMedPubMedCentralCrossRef Rastogi S, Sharov VG, Mishra S, Gupta RC, Blackburn B, Belardinelli L, Stanley WC, Sabbah HN. Ranolazine combined with enalapril or metoprolol prevents progressive LV dysfunction and remodeling in dogs with moderate heart failure. Am J Physiol Heart Circ Physiol. 2008;295:H2149–55.PubMedPubMedCentralCrossRef
107.
Zurück zum Zitat 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;49:1027–34.PubMedCrossRef 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;49:1027–34.PubMedCrossRef
108.
Zurück zum Zitat 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;16:216–21.PubMedCrossRef 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;16:216–21.PubMedCrossRef
109.
Zurück zum Zitat Cocco G, Rousseau MF, Bouvy T, Cheron P, Williams G, Detry JM, Pouleur H. Effects of a new metabolic modulator, ranolazine, on exercise tolerance in angina pectoris patients treated with beta-blocker or diltiazem. J Cardiovasc Pharmacol. 1992;20:131–8.PubMed Cocco G, Rousseau MF, Bouvy T, Cheron P, Williams G, Detry JM, Pouleur H. Effects of a new metabolic modulator, ranolazine, on exercise tolerance in angina pectoris patients treated with beta-blocker or diltiazem. J Cardiovasc Pharmacol. 1992;20:131–8.PubMed
110.
Zurück zum Zitat Venkataraman R, Belardinelli L, Blackburn B, Heo J, Iskandrian AE. A study of the effects of ranolazine using automated quantitative analysis of serial myocardial perfusion images. JACC Cardiovasc Imaging. 2009;2:1301–9.PubMedCrossRef Venkataraman R, Belardinelli L, Blackburn B, Heo J, Iskandrian AE. A study of the effects of ranolazine using automated quantitative analysis of serial myocardial perfusion images. JACC Cardiovasc Imaging. 2009;2:1301–9.PubMedCrossRef
111.
Zurück zum Zitat Timmis AD, Chaitman BR, Crager M. Effects of ranolazine on exercise tolerance and HbA1c in patients with chronic angina and diabetes. Eur Heart J. 2006;27:42–8.PubMedCrossRef Timmis AD, Chaitman BR, Crager M. Effects of ranolazine on exercise tolerance and HbA1c in patients with chronic angina and diabetes. Eur Heart J. 2006;27:42–8.PubMedCrossRef
112.
Zurück zum Zitat Arnold SV, McGuire DK, Spertus JA, Li Y, Yue P, Ben-Yehuda O, Belardinelli L, Jones PG, Olmsted A, Chaitman BR, Kosiborod M. Effectiveness of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina according to baseline hemoglobin A1c. Am Heart J. 2014;168:457–65 .e452PubMedCrossRef Arnold SV, McGuire DK, Spertus JA, Li Y, Yue P, Ben-Yehuda O, Belardinelli L, Jones PG, Olmsted A, Chaitman BR, Kosiborod M. Effectiveness of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina according to baseline hemoglobin A1c. Am Heart J. 2014;168:457–65 .e452PubMedCrossRef
113.
Zurück zum Zitat Kosiborod M, Arnold SV, Spertus JA, McGuire DK, Li Y, Yue P, Ben-Yehuda O, Katz A, Jones PG, Olmsted A, Belardinelli L, Chaitman BR. 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;61:2038–45.PubMedCrossRef Kosiborod M, Arnold SV, Spertus JA, McGuire DK, Li Y, Yue P, Ben-Yehuda O, Katz A, Jones PG, Olmsted A, Belardinelli L, Chaitman BR. 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;61:2038–45.PubMedCrossRef
114.
Zurück zum Zitat Villano A, Di Franco A, Nerla R, Sestito A, Tarzia P, Lamendola P, Di Monaco A, Sarullo FM, Lanza GA, Crea F. Effects of ivabradine and ranolazine in patients with microvascular angina pectoris. Am J Cardiol. 2013;112:8–13.PubMedCrossRef Villano A, Di Franco A, Nerla R, Sestito A, Tarzia P, Lamendola P, Di Monaco A, Sarullo FM, Lanza GA, Crea F. Effects of ivabradine and ranolazine in patients with microvascular angina pectoris. Am J Cardiol. 2013;112:8–13.PubMedCrossRef
115.
Zurück zum Zitat Tagliamonte E, Rigo F, Cirillo T, Astarita C, Quaranta G, Marinelli U, Caruso A, Romano C, Capuano N. Effects of ranolazine on noninvasive coronary flow Reserve in Patients with myocardial ischemia but without obstructive coronary artery disease. Echocardiography. 2015;32:516–21.PubMedCrossRef Tagliamonte E, Rigo F, Cirillo T, Astarita C, Quaranta G, Marinelli U, Caruso A, Romano C, Capuano N. Effects of ranolazine on noninvasive coronary flow Reserve in Patients with myocardial ischemia but without obstructive coronary artery disease. Echocardiography. 2015;32:516–21.PubMedCrossRef
116.
Zurück zum Zitat Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S, Wolff AA, Skene A, McCabe CH, Braunwald E. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007;297:1775–83.PubMedCrossRef Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S, Wolff AA, Skene A, McCabe CH, Braunwald E. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007;297:1775–83.PubMedCrossRef
117.
Zurück zum Zitat 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;6:9–16.PubMedCrossRef 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;6:9–16.PubMedCrossRef
118.
Zurück zum Zitat Mega JL, Hochman JS, Scirica BM, Murphy SA, Sloan S, McCabe CH, Merlini P, Morrow DA. Clinical features and outcomes of women with unstable ischemic heart disease: observations from metabolic efficiency with ranolazine for less ischemia in non-ST-elevation acute coronary syndromes-thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36). Circulation. 2010;121:1809–17.PubMedCrossRef Mega JL, Hochman JS, Scirica BM, Murphy SA, Sloan S, McCabe CH, Merlini P, Morrow DA. Clinical features and outcomes of women with unstable ischemic heart disease: observations from metabolic efficiency with ranolazine for less ischemia in non-ST-elevation acute coronary syndromes-thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36). Circulation. 2010;121:1809–17.PubMedCrossRef
119.
Zurück zum Zitat Karwatowska-Prokopczuk E, Wang W, Cheng ML, Zeng D, Schwartz PJ, Belardinelli L. The risk of sudden cardiac death in patients with non-ST elevation acute coronary syndrome and prolonged QTc interval: effect of ranolazine. Europace. 2013;15:429–36.PubMedCrossRef Karwatowska-Prokopczuk E, Wang W, Cheng ML, Zeng D, Schwartz PJ, Belardinelli L. The risk of sudden cardiac death in patients with non-ST elevation acute coronary syndrome and prolonged QTc interval: effect of ranolazine. Europace. 2013;15:429–36.PubMedCrossRef
120.
Zurück zum Zitat Morrow DA, Scirica BM, Sabatine MS, de Lemos JA, Murphy SA, Jarolim P, Theroux P, Bode C, Braunwald E. B-type natriuretic peptide and the effect of ranolazine in patients with non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 (metabolic efficiency with ranolazine for less ischemia in non-ST elevation acute coronary-thrombolysis in myocardial infarction 36) trial. J Am Coll Cardiol. 2010;55:1189–96.PubMedCrossRef Morrow DA, Scirica BM, Sabatine MS, de Lemos JA, Murphy SA, Jarolim P, Theroux P, Bode C, Braunwald E. B-type natriuretic peptide and the effect of ranolazine in patients with non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 (metabolic efficiency with ranolazine for less ischemia in non-ST elevation acute coronary-thrombolysis in myocardial infarction 36) trial. J Am Coll Cardiol. 2010;55:1189–96.PubMedCrossRef
121.
Zurück zum Zitat Chisholm JW, Goldfine AB, Dhalla AK, Braunwald E, Morrow DA, Karwatowska-Prokopczuk E, Belardinelli L. Effect of ranolazine on A1C and glucose levels in hyperglycemic patients with non-ST elevation acute coronary syndrome. Diabetes Care. 2010;33:1163–8.PubMedPubMedCentralCrossRef Chisholm JW, Goldfine AB, Dhalla AK, Braunwald E, Morrow DA, Karwatowska-Prokopczuk E, Belardinelli L. Effect of ranolazine on A1C and glucose levels in hyperglycemic patients with non-ST elevation acute coronary syndrome. Diabetes Care. 2010;33:1163–8.PubMedPubMedCentralCrossRef
122.
Zurück zum Zitat Antzelevitch C, Burashnikov A, Sicouri S, Belardinelli L. Electrophysiologic basis for the antiarrhythmic actions of ranolazine. Heart Rhythm. 2011;8:1281–90.PubMedPubMedCentralCrossRef Antzelevitch C, Burashnikov A, Sicouri S, Belardinelli L. Electrophysiologic basis for the antiarrhythmic actions of ranolazine. Heart Rhythm. 2011;8:1281–90.PubMedPubMedCentralCrossRef
123.
Zurück zum Zitat Bunch TJ, Mahapatra S, Murdock D, Molden J, Weiss JP, May HT, Bair TL, Mader KM, Crandall BG, Day JD, Osborn JS, Muhlestein JB, Lappe DL, Anderson JL. Ranolazine reduces ventricular tachycardia burden and ICD shocks in patients with drug-refractory ICD shocks. Pacing Clin Electrophysiol. 2011;34:1600–6.PubMedCrossRef Bunch TJ, Mahapatra S, Murdock D, Molden J, Weiss JP, May HT, Bair TL, Mader KM, Crandall BG, Day JD, Osborn JS, Muhlestein JB, Lappe DL, Anderson JL. Ranolazine reduces ventricular tachycardia burden and ICD shocks in patients with drug-refractory ICD shocks. Pacing Clin Electrophysiol. 2011;34:1600–6.PubMedCrossRef
124.
Zurück zum Zitat Frommeyer G, Rajamani S, Grundmann F, Stypmann J, Osada N, Breithardt G, Belardinelli L, Eckardt L, Milberg P. New insights into the beneficial electrophysiologic profile of ranolazine in heart failure: prevention of ventricular fibrillation with increased postrepolarization refractoriness and without drug-induced proarrhythmia. J Card Fail. 2012;18:939–49.PubMedCrossRef Frommeyer G, Rajamani S, Grundmann F, Stypmann J, Osada N, Breithardt G, Belardinelli L, Eckardt L, Milberg P. New insights into the beneficial electrophysiologic profile of ranolazine in heart failure: prevention of ventricular fibrillation with increased postrepolarization refractoriness and without drug-induced proarrhythmia. J Card Fail. 2012;18:939–49.PubMedCrossRef
125.
Zurück zum Zitat Sabbah HN, Chandler MP, Mishima T, Suzuki G, Chaudhry P, Nass O, Biesiadecki BJ, Blackburn B, Wolff A, Stanley WC. Ranolazine, a partial fatty acid oxidation (pFOX) inhibitor, improves left ventricular function in dogs with chronic heart failure. J Card Fail. 2002;8:416–22.PubMedCrossRef Sabbah HN, Chandler MP, Mishima T, Suzuki G, Chaudhry P, Nass O, Biesiadecki BJ, Blackburn B, Wolff A, Stanley WC. Ranolazine, a partial fatty acid oxidation (pFOX) inhibitor, improves left ventricular function in dogs with chronic heart failure. J Card Fail. 2002;8:416–22.PubMedCrossRef
126.
Zurück zum Zitat Aaker A, McCormack JG, Hirai T, Musch TI. Effects of ranolazine on the exercise capacity of rats with chronic heart failure induced by myocardial infarction. J Cardiovasc Pharmacol. 1996;28:353–62.PubMedCrossRef Aaker A, McCormack JG, Hirai T, Musch TI. Effects of ranolazine on the exercise capacity of rats with chronic heart failure induced by myocardial infarction. J Cardiovasc Pharmacol. 1996;28:353–62.PubMedCrossRef
127.
Zurück zum Zitat Sossalla S, Wagner S, Rasenack EC, Ruff H, Weber SL, Schondube FA, Tirilomis T, Tenderich G, Hasenfuss G, Belardinelli L, Maier LS. Ranolazine improves diastolic dysfunction in isolated myocardium from failing human hearts--role of late sodium current and intracellular ion accumulation. J Mol Cell Cardiol. 2008;45:32–43.PubMedCrossRef Sossalla S, Wagner S, Rasenack EC, Ruff H, Weber SL, Schondube FA, Tirilomis T, Tenderich G, Hasenfuss G, Belardinelli L, Maier LS. Ranolazine improves diastolic dysfunction in isolated myocardium from failing human hearts--role of late sodium current and intracellular ion accumulation. J Mol Cell Cardiol. 2008;45:32–43.PubMedCrossRef
128.
Zurück zum Zitat Hale SL, Shryock JC, Belardinelli L, Sweeney M, Kloner RA. Late sodium current inhibition as a new cardioprotective approach. J Mol Cell Cardiol. 2008;44:954–67.PubMedCrossRef Hale SL, Shryock JC, Belardinelli L, Sweeney M, Kloner RA. Late sodium current inhibition as a new cardioprotective approach. J Mol Cell Cardiol. 2008;44:954–67.PubMedCrossRef
129.
Zurück zum Zitat Wu Y, Song Y, Belardinelli L, Shryock JC. The late Na + current (INa) inhibitor ranolazine attenuates effects of palmitoyl-L-carnitine to increase late INa and cause ventricular diastolic dysfunction. J Pharmacol Exp Ther. 2009;330:550–7.PubMedCrossRef Wu Y, Song Y, Belardinelli L, Shryock JC. The late Na + current (INa) inhibitor ranolazine attenuates effects of palmitoyl-L-carnitine to increase late INa and cause ventricular diastolic dysfunction. J Pharmacol Exp Ther. 2009;330:550–7.PubMedCrossRef
130.
Zurück zum Zitat Fragasso G, Spoladore R, Cuko A, Palloshi A. Modulation of fatty acids oxidation in heart failure by selective pharmacological inhibition of 3-ketoacyl coenzyme-a thiolase. Curr Clin Pharmacol. 2007;2:190–6.PubMedCrossRef Fragasso G, Spoladore R, Cuko A, Palloshi A. Modulation of fatty acids oxidation in heart failure by selective pharmacological inhibition of 3-ketoacyl coenzyme-a thiolase. Curr Clin Pharmacol. 2007;2:190–6.PubMedCrossRef
131.
Zurück zum Zitat Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, Bugiardini R, Crea F, Cuisset T, Di Mario C, Ferreira JR, Gersh BJ, Gitt AK, Hulot JS, Marx N, Opie LH, Pfisterer M, Prescott E, Ruschitzka F, Sabate M, Senior R, Taggart DP, van der Wall EE, Vrints CJ, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Knuuti J, Valgimigli M, Bueno H, Claeys MJ, Donner-Banzhoff N, Erol C, Frank H, Funck-Brentano C, Gaemperli O, Gonzalez-Juanatey JR, Hamilos M, Hasdai D, Husted S, James SK, Kervinen K, Kolh P, Kristensen SD, Lancellotti P, Maggioni AP, Piepoli MF, Pries AR, Romeo F, Ryden L, Simoons ML, Sirnes PA, Steg PG, Timmis A, Wijns W, Windecker S, Yildirir A, Zamorano JL. 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.PubMedCrossRef Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, Bugiardini R, Crea F, Cuisset T, Di Mario C, Ferreira JR, Gersh BJ, Gitt AK, Hulot JS, Marx N, Opie LH, Pfisterer M, Prescott E, Ruschitzka F, Sabate M, Senior R, Taggart DP, van der Wall EE, Vrints CJ, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Knuuti J, Valgimigli M, Bueno H, Claeys MJ, Donner-Banzhoff N, Erol C, Frank H, Funck-Brentano C, Gaemperli O, Gonzalez-Juanatey JR, Hamilos M, Hasdai D, Husted S, James SK, Kervinen K, Kolh P, Kristensen SD, Lancellotti P, Maggioni AP, Piepoli MF, Pries AR, Romeo F, Ryden L, Simoons ML, Sirnes PA, Steg PG, Timmis A, Wijns W, Windecker S, Yildirir A, Zamorano JL. 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.PubMedCrossRef
132.
Metadaten
Titel
Pharmacological Agents Targeting Myocardial Metabolism for the Management of Chronic Stable Angina : an Update
verfasst von
Giacinta Guarini
Alda Huqi
Doralisa Morrone
Mario Marzilli
Publikationsdatum
06.08.2016
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 4/2016
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-016-6677-y

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