cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLC10.15829/1728-8800-2013-1-102-110cardiovascular-128Research ArticleОБЗОРЫREVIEWSВОЗМОЖНОСТИ СОВРЕМЕННОГО ИНГИБИТОРА АНГИОТЕНЗИН-ПРЕВРАЩАЮЩЕГО ФЕРМЕНТА ЗОФЕНОПРИЛА В КЛИНИЧЕСКОЙ ПРАКТИКЕ: КАРДИОПРОТЕКТИВНЫЕ, АНТИИШЕМИЧЕСКИЕ И АНТИАТЕРОГЕННЫЕ ЭФФЕКТЫPOTENTIAL OF THE MODERN ACE INHIBITOR ZOFENOPRIL IN CLINICAL PRACTICE: CARDIOPROTECTIVE, ANTI-ISCHEMIC, AND ANTIATHEROGENIC EFFECTSБубноваМ. Г.BubnovaM. G.

д.м.н., профессор, руководитель отдела реабилитации и вторичной профилактики сочетанной патологии с лабораторией профилактики атеросклероза и тромбоза

mbubnova@gnicpm.ruФГБУ «Государственный научно-исследовательский центр профилактической медицины» Минздрава России, МоскваРоссияState Research Centre for Preventive Medicine, MoscowRussian Federation201320022013121102110Copyright © Бубнова М.Г., 20132013Бубнова М.Г.Bubnova M.G.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/128

В представленном обзоре обсуждаются вопросы назначения ингибиторов ангиотензин-превращающего фермента (ИАПФ) у больных сердечно-сосудистыми заболеваниями (ССЗ), в т.ч. перенесших острый инфаркт миокарда (ИМ). Особый акцент делается на современном ИАПФ — зофеноприле. Обсуждаются его особые фармакологические свойства, рассматриваются дополнительные эффекты, связанные с кардиопротекцией, антиишемическим и антиатерогенным влияниями. Дается обоснование клинической эффективности зофеноприла и возможности его более широкого использования в клинической практике. 

The review discusses various aspects of angiotensin-converting enzyme (ACE) inhibitor therapy in patients with cardiovascular disease (CVD), including acute myocardial infarction (AMI). The focus is on the modern ACE inhibitor zofenopril, its specific pharmacological characteristics, and additional cardioprotective, anti-ischemic, and antiatherogenic effects. The existing evidence of clinical effectiveness of zofenopril and its potential for a wider use in clinical practice are also addressed. 

инфаркт миокардазофеноприлкардиопротекцияmyocardial infarctionzofenoprilcardioprotectionReferencesMak T, Freedman AM, Dickens BF, et al. Protective effects of sulphydrylcontaining angiotensin converting enzyme inhibitors against free radical injury in endothelial cells. Biochemical. Pharmacology 1990; 40 (9): 2169–75.Mak T, Freedman AM, Dickens BF, et al. Protective effects of sulphydrylcontaining angiotensin converting enzyme inhibitors against free radical injury in endothelial cells. Biochemical. Pharmacology 1990; 40 (9): 2169–75.Sun Y, Mendelsohn FA. Angiotensin converting enzyme inhibition in heart, kidney, and serum studied ex vivo after administration of zofenopril, captopril, and lisinopril. J Cardiovasc Pharmacol 1991; 18 (4): 478–86.Sun Y, Mendelsohn FA. Angiotensin converting enzyme inhibition in heart, kidney, and serum studied ex vivo after administration of zofenopril, captopril, and lisinopril. J Cardiovasc Pharmacol 1991; 18 (4): 478–86.Van Gilst WH, De Graeff PA, De Leeue MJ, et al. Converting enzyme inhibitors and the role of sulphydryl group in the potentiation of exo- and endogeneous nitrovasodilatators. J Cardiovasc Pharmacol 1991; 18: 429–36.Van Gilst WH, De Graeff PA, De Leeue MJ, et al. Converting enzyme inhibitors and the role of sulphydryl group in the potentiation of exo- and endogeneous nitrovasodilatators. J Cardiovasc Pharmacol 1991; 18: 429–36.De Graef PA, Van Gilst WH. The effect of bradikinin on coronary flow and its potentiation by SH-containing ACE-inhibitors. Recent Prog Kinins 1992; 38: 110–8.De Graef PA, Van Gilst WH. The effect of bradikinin on coronary flow and its potentiation by SH-containing ACE-inhibitors. Recent Prog Kinins 1992; 38: 110–8.Sacco G, Bigioni M, Evangelista S, et al. Cardioprotective effects of zofenopril, a new angiotensin-converting enzyme inhibitor, on doxorubicin-induced cardiotoxicity in the rat. Eur J Pharmacol 2001; 414: 71–8.Sacco G, Bigioni M, Evangelista S, et al. Cardioprotective effects of zofenopril, a new angiotensin-converting enzyme inhibitor, on doxorubicin-induced cardiotoxicity in the rat. Eur J Pharmacol 2001; 414: 71–8.Grover GJ, Sleph PG, Dzwonczyk S, et al. Effects of different angiotensin￾converting enzyme (ACE) inhibitors on ischemic isolated rat hearts: relationship between cardiac ACE inhibition and cardioprotection. J Pharmacol Exp Ther 1991; 257: 919–29.Grover GJ, Sleph PG, Dzwonczyk S, et al. Effects of different angiotensin￾converting enzyme (ACE) inhibitors on ischemic isolated rat hearts: relationship between cardiac ACE inhibition and cardioprotection. J Pharmacol Exp Ther 1991; 257: 919–29.Liu X, Engelman RM, Ronson JA, et al. Attenuation of myocardial reperfusion injury by sulfhydryl-containing angiotensin converting enzyme inhibitors. Cardiovasc Drugs Ther 1992; 6: 437–43.Liu X, Engelman RM, Ronson JA, et al. Attenuation of myocardial reperfusion injury by sulfhydryl-containing angiotensin converting enzyme inhibitors. Cardiovasc Drugs Ther 1992; 6: 437–43.Ferrari R, Cargnoni S, Curello C, et al. Protection of the ischemic myocardium by the converting-enzyme inhibitor zofenopril: Insight into its mechanism of action. J Cardiovasc Pharmacol 1992; 20: 694–704.Ferrari R, Cargnoni S, Curello C, et al. Protection of the ischemic myocardium by the converting-enzyme inhibitor zofenopril: Insight into its mechanism of action. J Cardiovasc Pharmacol 1992; 20: 694–704.Frascarelli S, Ghelardoni S, Ronca-Testoni S, et al. Cardioprotective effect of zofenopril inperfused rat heart subjected to ischemia and reperfusion. J Cardiovasc Pharmacol 2004; 43: 294–9.Frascarelli S, Ghelardoni S, Ronca-Testoni S, et al. Cardioprotective effect of zofenopril inperfused rat heart subjected to ischemia and reperfusion. J Cardiovasc Pharmacol 2004; 43: 294–9.Przyklenk K, Kloner RA. Angiotensin converting enzyme inhibitors improved contractile function of stunned myocardium by different mechanisms of action. Am Heart J 1991; 121: 1319–30.Przyklenk K, Kloner RA. Angiotensin converting enzyme inhibitors improved contractile function of stunned myocardium by different mechanisms of action. Am Heart J 1991; 121: 1319–30.Pfeffer MA, Pfeffer JM, Steinberg CR, et al. Survival after an experimental myocardial infarction: beneficial effects of long-term therapy with captopril. Circulation 1985; 72: 406–12.Pfeffer MA, Pfeffer JM, Steinberg CR, et al. Survival after an experimental myocardial infarction: beneficial effects of long-term therapy with captopril. Circulation 1985; 72: 406–12.Sweet CS, Emmert SE, Stabilito II, et al. Increased survival in rats with congestive heart failure treated with enalapril. J Cardiovasc Pharmacol 1987; 10: 636–42.Sweet CS, Emmert SE, Stabilito II, et al. Increased survival in rats with congestive heart failure treated with enalapril. J Cardiovasc Pharmacol 1987; 10: 636–42.Pinto YM, Van Wijngaarden J, Van Gilst WH, et al. The effects of shortand long-term treatment with an ACE-inhibitorin rats with myocardial infarction. Basic Res Cardiol 1991; 86 (Suppl. 1): 165–72.Pinto YM, Van Wijngaarden J, Van Gilst WH, et al. The effects of shortand long-term treatment with an ACE-inhibitorin rats with myocardial infarction. Basic Res Cardiol 1991; 86 (Suppl. 1): 165–72.McDonald KM, Garr M, Carlyle PF, et al. Relative effects of alpha 1-adrenoceptor blockade, converting enzyme inhibitor therapy, and angiotensin II subtype 1 receptor blockade on ventricular remodeling in the dog. Circulation 1994; 90: 3034–46.McDonald KM, Garr M, Carlyle PF, et al. Relative effects of alpha 1-adrenoceptor blockade, converting enzyme inhibitor therapy, and angiotensin II subtype 1 receptor blockade on ventricular remodeling in the dog. Circulation 1994; 90: 3034–46.Tio AR, de Langen CD, de Graeff PA, et al. The effects of oral pretreatment with zofenopril, an angiotensin-converting enzyme inhibitor, on early reperfusion and subsequent electrophysiologic stability in the pig. Cardiovasc Drug Ther 1990; 4: 695–704.Tio AR, de Langen CD, de Graeff PA, et al. The effects of oral pretreatment with zofenopril, an angiotensin-converting enzyme inhibitor, on early reperfusion and subsequent electrophysiologic stability in the pig. Cardiovasc Drug Ther 1990; 4: 695–704.Grassi G, Seravalle G, Bertinieri G, et al. Behaviour of the adrenergic cardiovascular drive in atrial fibrillation and cardiac arrhythmias. Acta Physiol Scand 2003;177: 399–404.Grassi G, Seravalle G, Bertinieri G, et al. Behaviour of the adrenergic cardiovascular drive in atrial fibrillation and cardiac arrhythmias. Acta Physiol Scand 2003;177: 399–404.Subissi A, Evangelista S, Giachetti A. Preclinical profile of zofenopril: an angiotensin converting enzyme inhibitor with peculiar cardioprotective properties. Cardiovasc Drug Rev 1999; 17: 115–33.Subissi A, Evangelista S, Giachetti A. Preclinical profile of zofenopril: an angiotensin converting enzyme inhibitor with peculiar cardioprotective properties. Cardiovasc Drug Rev 1999; 17: 115–33.Scribner AW, Loscalzo J, Napoli C, et al. The effect of angiotensinconverting enzyme inhibition on endothelial function and oxidant stress. Eur J Pharmacol 2003; 482: 95–9.Scribner AW, Loscalzo J, Napoli C, et al. The effect of angiotensinconverting enzyme inhibition on endothelial function and oxidant stress. Eur J Pharmacol 2003; 482: 95–9.Buikema H, Monnink SH, Tio RA, et al. Comparison of zofenopril and lisinopril to study the role of the sulfhydrylgroup in improvement of endothelial dysfunction with ACE-inhibitors in experimental heart failure. Br J Pharmacol 2000; 130 (8): 1999–2007.Buikema H, Monnink SH, Tio RA, et al. Comparison of zofenopril and lisinopril to study the role of the sulfhydrylgroup in improvement of endothelial dysfunction with ACE-inhibitors in experimental heart failure. Br J Pharmacol 2000; 130 (8): 1999–2007.Subissi A, Evangelista S, Giachetti A. Preclinical profile of zofenopril: an angiotensin converting enzyme inhibitor with peculiar cardioprotective properties. Cardiovasc Drug Rev1999; 17: 115–33.Subissi A, Evangelista S, Giachetti A. Preclinical profile of zofenopril: an angiotensin converting enzyme inhibitor with peculiar cardioprotective properties. Cardiovasc Drug Rev1999; 17: 115–33.Brogelli L, Parenti A, Capaccioli S, et al. The angiotensin convetring enzyme inhibitor zofenoprilat prevents endothelial cell apoptosis and promotes coronary angiogenesis in vitro. FASEB J 1999; 13: A528.Brogelli L, Parenti A, Capaccioli S, et al. The angiotensin convetring enzyme inhibitor zofenoprilat prevents endothelial cell apoptosis and promotes coronary angiogenesis in vitro. FASEB J 1999; 13: A528.Napoli C, Sica V, de Nigris F, et al. Sulfhydryl angiotensin-converting enzyme inhibition induces sustained reduction of systemic oxidative stress and improves the nitric oxide pathway in patients with essential hypertension. Am Heart J 2004; 148 (1): е 5.Napoli C, Sica V, de Nigris F, et al. Sulfhydryl angiotensin-converting enzyme inhibition induces sustained reduction of systemic oxidative stress and improves the nitric oxide pathway in patients with essential hypertension. Am Heart J 2004; 148 (1): е 5.Pasini AF, Garbin U, Nava MC, et al. Effect of sulfhydryl and non-sulfhydryl angiotensin-converting enzyme inhibitors on endothelial function in essential hypertensive patients. Am J Hypertens 2007; 20: 443–50. 24. Cominacini L, Pasini A, Garbin U, et al. Zofenopril inhibits the expression of adhesion molecules on endothelial cells by reducing reactive oxygen species. Am J Hypertens 2002; 15: 891–5.Pasini AF, Garbin U, Nava MC, et al. Effect of sulfhydryl and non-sulfhydryl angiotensin-converting enzyme inhibitors on endothelial function in essential hypertensive patients. Am J Hypertens 2007; 20: 443–50. 24. Cominacini L, Pasini A, Garbin U, et al. Zofenopril inhibits the expression of adhesion molecules on endothelial cells by reducing reactive oxygen species. Am J Hypertens 2002; 15: 891–5.Scribner AW, Loscalzo J, Napoli C. The effect of angiotensin-converting enzymeinhibition on endothelial function and oxidant stress. Eur J Pharmacol 2003; 482: 95–9.Scribner AW, Loscalzo J, Napoli C. The effect of angiotensin-converting enzymeinhibition on endothelial function and oxidant stress. Eur J Pharmacol 2003; 482: 95–9.Subissi A, Evangelista S, Giachetti A. Preclinical Profile of Zofenopril: An angiotensin converting enzyme inhibitor with peculiar cardioprotective properties. Cardiovascular. Drug Reviews 1999; 17 (2): 115–33.Subissi A, Evangelista S, Giachetti A. Preclinical Profile of Zofenopril: An angiotensin converting enzyme inhibitor with peculiar cardioprotective properties. Cardiovascular. Drug Reviews 1999; 17 (2): 115–33.Napoli C, Bruzzese G, Ignarro LJ, et al. Long-term treatment with sulfhydryl angiotensin-converting enzyme inhibition reduces carotid intima-media thickening and improvesthe nitric oxide/oxidative stress pathways in newly diagnosed patients with mild to moderate primary hypertension. Am Heart J 2008; 156: 1154.e1–8.Napoli C, Bruzzese G, Ignarro LJ, et al. Long-term treatment with sulfhydryl angiotensin-converting enzyme inhibition reduces carotid intima-media thickening and improvesthe nitric oxide/oxidative stress pathways in newly diagnosed patients with mild to moderate primary hypertension. Am Heart J 2008; 156: 1154.e1–8.Pasini AF, Garbin U, Nava MC, et al. Effect of sulfhydryl and non-sulfhydryl angiotensin-converting enzyme inhibitors on endothelial function in essential hypertensive patients.Am J Hypertens 2007; 20: 443–50.Pasini AF, Garbin U, Nava MC, et al. Effect of sulfhydryl and non-sulfhydryl angiotensin-converting enzyme inhibitors on endothelial function in essential hypertensive patients.Am J Hypertens 2007; 20: 443–50.Lacourciere Y, Provencher P. Comparative effects of zofenopril and hydrochlorothiazide on office and ambulatory blood pressures in mild to moderate essential hypertension.Br J Clin Pharmacol 1989; 27: 371–6.Lacourciere Y, Provencher P. Comparative effects of zofenopril and hydrochlorothiazide on office and ambulatory blood pressures in mild to moderate essential hypertension.Br J Clin Pharmacol 1989; 27: 371–6.Borghi C, Ambrosioni E. Survival of Myocardial Infarction Long-term Evaluation Study Group. Effects of zofenopril on myocardial ischemia in post-myocardial infarction patients with preserved left ventricular function: the Survival of Myocardial Infarction Long-term Evaluation (SMILE) -ISCHEMIA study. Am Heart J 2007; 153 (3): 445.e7–14.Borghi C, Ambrosioni E. Survival of Myocardial Infarction Long-term Evaluation Study Group. Effects of zofenopril on myocardial ischemia in post-myocardial infarction patients with preserved left ventricular function: the Survival of Myocardial Infarction Long-term Evaluation (SMILE) -ISCHEMIA study. Am Heart J 2007; 153 (3): 445.e7–14.Flather M, Yusuf S, Kober L, et al. For the ACE-inhibitor Myocardial Infarction Collaborative Group. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. Lancet 2000; 355: 1575–81.Flather M, Yusuf S, Kober L, et al. For the ACE-inhibitor Myocardial Infarction Collaborative Group. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. Lancet 2000; 355: 1575–81.Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico). GISSI-3. Effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6 week mortality and ventricular function after acute myocardial infarction. Lancet 1994; 343: 1115–22.Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico). GISSI-3. Effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6 week mortality and ventricular function after acute myocardial infarction. Lancet 1994; 343: 1115–22.Fourth International Study of Infarct Survival Collaborative Group. ISIS-IV: a randomized factorial trial assessing early oral captopril. Oral mononitrate and intravenous magnesium sulphate in 58050 patients with suspected acute myocardial infarction. Lancet 1995; 345: 669–85.Fourth International Study of Infarct Survival Collaborative Group. ISIS-IV: a randomized factorial trial assessing early oral captopril. Oral mononitrate and intravenous magnesium sulphate in 58050 patients with suspected acute myocardial infarction. Lancet 1995; 345: 669–85.Borghi C, Bacchelli S, Degli Esposti D, Ambrosioni E. A review of the angiotensin-converting enzyme inhibitor, zofenopril, in the treatment of cardiovascular diseases. Expert Opin Pharmacother 2004; 5 (9): 1965–77.Borghi C, Bacchelli S, Degli Esposti D, Ambrosioni E. A review of the angiotensin-converting enzyme inhibitor, zofenopril, in the treatment of cardiovascular diseases. Expert Opin Pharmacother 2004; 5 (9): 1965–77.Ambrosioni E, Borghi C, Magnani B. Early treatment of acute myocardial infarction with angiotensin-converting enzyme inhibition: safety considerations. SMILE pilot study working party. Am J Cardiol 1991; 68 (14):101D-10.Ambrosioni E, Borghi C, Magnani B. Early treatment of acute myocardial infarction with angiotensin-converting enzyme inhibition: safety considerations. SMILE pilot study working party. Am J Cardiol 1991; 68 (14):101D-10.Ambrosioni E, Borghi C, Magnani B, et al. for the Survival of Myocardial Infarction Long-term Evaluation (SMILE) study investigators. The effect of the angiotension-converting enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. New Engl J Med 1995; 332: 80–5.Ambrosioni E, Borghi C, Magnani B, et al. for the Survival of Myocardial Infarction Long-term Evaluation (SMILE) study investigators. The effect of the angiotension-converting enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. New Engl J Med 1995; 332: 80–5.Cushman DW, Wang FL, Fung WC, et al. Comparisons in vitro, ex vivo, and in vivo of the actions of seven structurally diverse inhibitors of angiotensin converting enzyme (ACE). Br J Clin Pharmacol 1989; 28 (Suppl 2): 115S-30.Cushman DW, Wang FL, Fung WC, et al. Comparisons in vitro, ex vivo, and in vivo of the actions of seven structurally diverse inhibitors of angiotensin converting enzyme (ACE). Br J Clin Pharmacol 1989; 28 (Suppl 2): 115S-30.Borghi C, Bacchelli S, Degli Esposti D, Ambrosioni E. A review of the angiotensin-converting enzyme inhibitor, zofenopril, in the treatment of cardiovascular diseases. Expert Opin Pharmacother 2004; 5 (9): 1965–77.Borghi C, Bacchelli S, Degli Esposti D, Ambrosioni E. A review of the angiotensin-converting enzyme inhibitor, zofenopril, in the treatment of cardiovascular diseases. Expert Opin Pharmacother 2004; 5 (9): 1965–77.Cushman DW, Wang FL, Fung WC, et al. Differentiation of angiotensin-converting enzyme (ACE) inhibitors by their selective inhibition of ACE in physiologically important target organs. Am J Hypertens 1989; 2 (4): 294–306.Cushman DW, Wang FL, Fung WC, et al. Differentiation of angiotensin-converting enzyme (ACE) inhibitors by their selective inhibition of ACE in physiologically important target organs. Am J Hypertens 1989; 2 (4): 294–306.Borghi C, Ambrosioni E. Survival of Myocardial Infarction Long-term Evaluation-2 Working Party.Double-blind comparison between zofenopril and lisinopril in patients with acute myocardial infarction: results of the Survival of Myocardial Infarction Long-term Evaluation-2 (SMILE-2) study. Am Heart J 2003; 145 (1): 80–7.Borghi C, Ambrosioni E. Survival of Myocardial Infarction Long-term Evaluation-2 Working Party.Double-blind comparison between zofenopril and lisinopril in patients with acute myocardial infarction: results of the Survival of Myocardial Infarction Long-term Evaluation-2 (SMILE-2) study. Am Heart J 2003; 145 (1): 80–7.Kobalava JD, Kijakbaev GK. Zofenopril. Clinical and pharmacological aspects. Moscow, MedExpertPress 2006. Russian (Кобалава Ж.Д., Киякбаев Г.К. Зофеноприл. Клинико-фармакологические аспекты. Москва, ООО «МедЭкспертПресс» 2006).Kobalava JD, Kijakbaev GK. Zofenopril. Clinical and pharmacological aspects. Moscow, MedExpertPress 2006. Russian (Кобалава Ж.Д., Киякбаев Г.К. Зофеноприл. Клинико-фармакологические аспекты. Москва, ООО «МедЭкспертПресс» 2006).Agostoni A, Gardinali M, Frangi D, et al. Activation of complement and kinin systems after thrombolytic therapy in patients with acute myocardial infarction. A comparison between streptokinase and recombinant tissue type plasminogen activator. Circulation 1994; 90 (6): 2666–70.Agostoni A, Gardinali M, Frangi D, et al. Activation of complement and kinin systems after thrombolytic therapy in patients with acute myocardial infarction. A comparison between streptokinase and recombinant tissue type plasminogen activator. Circulation 1994; 90 (6): 2666–70.Buikema H, Monnink SH, Tio RA, et al. Comparison of zofenopril and lisinopril to study the role of the sulfhydrylgroup in improvement of endothelial dysfunction with ACE-inhibitors in experimental heart failure. Br J Pharmacol 2000; 130 (8): 1999–2007.Buikema H, Monnink SH, Tio RA, et al. Comparison of zofenopril and lisinopril to study the role of the sulfhydrylgroup in improvement of endothelial dysfunction with ACE-inhibitors in experimental heart failure. Br J Pharmacol 2000; 130 (8): 1999–2007.Borghi C, Bacchelli S, Esposti DD, et al. Effects of the administration of an angiotensinconverting enzyme inhibitor during the acutephase of myocardial infarction in patients with arterial hypertension. SMILE Study Investigators. Am J Hypertens 1999; 12: 665–72.Borghi C, Bacchelli S, Esposti DD, et al. Effects of the administration of an angiotensinconverting enzyme inhibitor during the acutephase of myocardial infarction in patients with arterial hypertension. SMILE Study Investigators. Am J Hypertens 1999; 12: 665–72.Borghi C, Bacchelli S, Esposti DD, et al. Effects of the Early ACE-Inhibition in Diabetic Nonthrombolyzed Patients With Anterior Acute Myocardial Infarction. Diabetes Care 2003; 26 (6): 1862–8.Borghi C, Bacchelli S, Esposti DD, et al. Effects of the Early ACE-Inhibition in Diabetic Nonthrombolyzed Patients With Anterior Acute Myocardial Infarction. Diabetes Care 2003; 26 (6): 1862–8.Borghi C, Cicero AFG, Ambrosioni E. onbehalf of the Survival of Myocardial InfarctionLong-term Evaluation (SMILE) Study. Effects of early treatment with zofenopril in patients with myocardialinfarction and metabolic syndrome: the SMILE study. Vasc Health Risk Manag 2008; 4 (3): 665–71.Borghi C, Cicero AFG, Ambrosioni E. onbehalf of the Survival of Myocardial InfarctionLong-term Evaluation (SMILE) Study. Effects of early treatment with zofenopril in patients with myocardialinfarction and metabolic syndrome: the SMILE study. Vasc Health Risk Manag 2008; 4 (3): 665–71.Ninomiya JK, L’Italien G, Criqui MH, et al. Association of the metabolic syndromewith history of myocardial infarction and stroke in the Third National Health and Nutrition Examination Survey. Circulation 2004; 109: 42–6.Ninomiya JK, L’Italien G, Criqui MH, et al. Association of the metabolic syndromewith history of myocardial infarction and stroke in the Third National Health and Nutrition Examination Survey. Circulation 2004; 109: 42–6.Borghi C, Cicero AF, Bacchelli S, et al. Serum cholesterol levels on admission and survival in patients with acute myocardial infarction treated with zofenopril: a post hoc analysis of the Survival of Myocardial Infarction Long-term Evaluation trial. Fundam Clin Pharmacol 2009; 23:641–8.Borghi C, Cicero AF, Bacchelli S, et al. Serum cholesterol levels on admission and survival in patients with acute myocardial infarction treated with zofenopril: a post hoc analysis of the Survival of Myocardial Infarction Long-term Evaluation trial. Fundam Clin Pharmacol 2009; 23:641–8.Jhund P, McMurray JJ. Does aspirin reduce the benefit of an angiotensinconverting enzyme inhibitor? Choosing between the Scylla of observational studies and the Charybdis of subgroup analysis. Circulation 2006; 113 (22): 2566–8.Jhund P, McMurray JJ. Does aspirin reduce the benefit of an angiotensinconverting enzyme inhibitor? Choosing between the Scylla of observational studies and the Charybdis of subgroup analysis. Circulation 2006; 113 (22): 2566–8.Dzau VJ, Antman EM, Black HR, et al. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part I: Pathophysiology and clinical trial evidence (risk factors through stable coronary artery disease). Circulation 2006; 114 (25): 2850–70.Dzau VJ, Antman EM, Black HR, et al. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part I: Pathophysiology and clinical trial evidence (risk factors through stable coronary artery disease). Circulation 2006; 114 (25): 2850–70.Latini R, Tognoni G, Maggioni AP, et al. Clinical effects of early angiotensin￾converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting Enzyme Inhibitor Myocardial Infarction Collaborative Group. JACC 2000; 35 (7): 1801–7.Latini R, Tognoni G, Maggioni AP, et al. Clinical effects of early angiotensin￾converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting Enzyme Inhibitor Myocardial Infarction Collaborative Group. JACC 2000; 35 (7): 1801–7.Borghi C, Ambrosioni E, Novo S, et al. Comparison between zofenopril and ramipril in combination with acetylsalicylic acid in patients with left ventricular systolic dysfunction after acute myocardial infarction: results of a randomized, double-blind, parallel-group, multicenter, European study (SMILE-4). Clin Cardiol 2012; 35 (7): 416–23.Borghi C, Ambrosioni E, Novo S, et al. Comparison between zofenopril and ramipril in combination with acetylsalicylic acid in patients with left ventricular systolic dysfunction after acute myocardial infarction: results of a randomized, double-blind, parallel-group, multicenter, European study (SMILE-4). Clin Cardiol 2012; 35 (7): 416–23.

The authors declare that there are no conflicts of interest present.