Одна из ключевых систем организма, влияющих на функционирование сердца и сосудов, – ренин-ангиотензин-альдостероновая система (РААС). Усиление активации РААС играет важную роль в развитии сердечно-сосудистых заболеваний. Доказано, что подавление активности РААС приводит к снижению частоты развития осложнений сердечно-сосудистых заболеваний и смертности от них. Кандесартан является селективным блокатором рецепторов ангиотензина II 1-го типа. Отличительными особенностями его фармакокинетики и фармакодинамики являются большая продолжительность антигипертензивного действия, высокая селективность и хорошая биодоступность препарата. В лечении артериальной гипертензии кандесартан способен эффективно предотвращать утренний подъем артериального давления. Для препарата свойственны церебро- и кардиопротективный эффекты, способность снижать риск появления новых случаев сахарного диабета. Препарат оказывается эффективным средством в лечении нефропатии разного генеза, в том числе и у больных с выраженным снижением функции почек. Метаболическая нейтральность, способность предотвращать развитие микро- и макроангиопатии позволяют рекомендовать этот блокатор рецепторов ангиотензина в лечении больных сахарным диабетом. Благоприятный профиль фармакокинетических свойств создает преимущество кандесартана в эффективности по сравнению с другими препаратами той же группы.
Ключевые слова: кандесартан, артериальная гипертензия, блокаторы рецепторов к ангиотензину II, хроническая сердечная недостаточность, сахарный диабет.
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One of the key systems of the body, affecting the functioning of the heart and blood vessels, – the renin-angiotensin-aldosterone system (RAAS). Amplification RAAS activation plays an important role in the development of cardiovascular diseases. It proved that inhibition of the RAAS activity reduces the incidence of complications of cardiovascular diseases and mortality. Candesartan is a selective blocker of angiotensin II receptor type 1. Distinctive features of its pharmacokinetics and pharmacodynamics are longer duration of antihypertensive action, high selectivity and good bioavailability. In the treatment of hypertension with candesartan is able to effectively prevent the early morning rise in blood pressure. For preparation characterized cerebro and cardioprotective effects, the ability to reduce the risk of new cases of diabetes. The drug is effective in the treatment of nephropathy different genesis, including patients with a severely reduced renal function. The metabolic neutrality, the ability to prevent the development of micro- and macroangiopathy allow us to recommend the angiotensin receptor blocker in the treatment of patients with diabetes mellitus. The favorable pharmacokinetic profile of the candesartan creates performance advantage compared to other drugs of the same group.
Key words: candesartan, hypertension, blocker of angiotensin II receptor, chronic heart failure, diabetes mellitus.
1. Евдокимова А.Г., Ложкина М.В., Коваленко Е.В., Евдокимов В.В. Клиническая эффективность ирбесартана у пациентов с сердечно-сосудистыми заболеваниями. Сердце. 2012; 11 (6): 364–8. / Evdokimova A.G., Lozhkina M.V., Kovalenko E.V. Evdokimov V.V. Klinicheskaia effektivnost' irbesartana u patsientov s serdechno-sosudistymi zabolevaniiami. Serdtse. 2012; 11 (6): 364–8. [in Russian]
2. Евдокимова А.Г., Ложкина М.В., Коваленко Е.В. Особенности применения кандесартана в клинической практике. Consilium Medicum. 2016; 18 (1): 54–9. / Evdokimova A.G., Lozhkina M.V., Kovalenko E.V. Osobennosti primeneniia kandesartana v klinicheskoi praktike. Consilium Medicum. 2016; 18 (1): 54–9. [in Russian]
3. Гиляревский С.Р., Голшмид М.В., Кузьмина И.М. Доказательная история кандесартана: прошлое, будущее и настоящее. Сердечная недостаточность. 2015; 16 (5): 303–10. / Giliarevskii S.R., Golshmid M.V., Kuz'mina I.M. Dokazatel'naia istoriia kandesartana: proshloe, budushchee i nastoiashchee. Serdechnaia nedostatochnost'. 2015; 16 (5): 303–10. [in Russian]
4. Раков А.А., Хохлов А.Л., Федоров В.Н. и др. Фармакоэпидемиология хронической сердечной недостаточности у амбулаторных больных. Качественная клиническая практика. 2003; 2: 40–3. / Rakov A.A., Khokhlov A.L., Fedorov V.N. i dr. Farmakoepidemiologiia khronicheskoi serdechnoi nedostatochnosti u ambulatornykh bol'nykh. Kachestvennaia klinicheskaia praktika. 2003; 2: 40–3. [in Russian]
5. Сиренко Ю.Н., Донченко Н.В. Место кандесартана в современной терапии сердечно-сосудистых заболеваний: обзор доказательств. Артериальная гипертензия. 2011; 4 (18): 114–26. / Sirenko Iu.N., Donchenko N.V. Mesto kandesartana v sovremennoi terapii serdechno-sosudistykh zabolevanii: obzor dokazatel'stv. Arterial'naia gipertenziia. 2011; 4 (18): 114–26. [in Russian]
6. Хохлов А.Л., Сироткина А.М., Могутова И.С. и др. Распространенность некоторых полиморфных вариантов генов у больных с артериальной гипертензией (материалы конференции «Кардиоваскулярная профилактика и реабилитация 2013», г. Москва). Кардиоваскулярная терапия и профилактика. 2013; 12: 41. / Khokhlov A.L., Sirotkina A.M., Mogutova I.S. i dr. Rasprostranennost' nekotorykh polimorfnykh variantov genov u bol'nykh s arterial'noi gipertenziei (materialy konferentsii “Kardiovaskuliarnaia profilaktika i reabilitatsiia 2013”, g. Moskva). Kardiovaskuliarnaia terapiia i profilaktika. 2013; 12: 41. [in Russian]
7. Шуникова М.И., Хохлов А.Л., Соснин А.Ю. Сравнительная оценка органопротективных свойств фозиноприла, амлодипина и метопролола у больных артериальной гипертонией. Consilium Medicum. 2008; 10 (11): 30–5. / Shunikova M.I., Khokhlov A.L., Sosnin A.Iu. Sravnitel'naia otsenka organoprotektivnykh svoistv fozinoprila, amlodipina i metoprolola u bol'nykh arterial'noi gipertoniei. Consilium Medicum. 2008; 10 (11): 30–5. [in Russian]
8. Abrahamsson Т, Karp L, Brabdl-Eliasson II el al. Candesartan causes long-last antagonism of angiotensin II receptor-mediated contractile effects in isolated vascular preparations: a comparison with irbesartan, losartan and its active metabolite (EXP-3174). Blood Pressure 2000; 9 (Abstr. Suppl.): 1–52.
9. Azilsartan medoxomil (Edarbi) the eighth ARB. Med Lett Drugs Ther 2011; 16 (53): 1364.
10. Bangalore S. Angiotensin receptor blockers and risk of myocardial infarction: meta-analyses and trial sequential analyses of 147 020 patients from randomised trials. BMJ 2011; 342: d2234.
11. Brunner HR, Gavras H, Laragh JH et al. Angiotensin-II blockade in man by Sar1-Ala8-angiotensin II for understanding and treatment of high blood pressure. Lancet 1973; 2: 1045.
12. Cuspidi C, Muiesan ML, Valagussa L еt al. Comparative effects of candesartan and enalapril on left ventricular hypertrophy in patients with essential hypertension: the candesartan assessment in the treatment of cardiac hypertrophy (CATCH) study. J Hypertens 2002; 20: 2293–300.
13. De Rosa ML, Chiariello M. Candesartan improves maximal exercise capacity in hypertensives: results of a randomized placebo-controlled crossover trial. J Clin Hypertens (Greenwich) 2009; 11 (4): 192–200.
14. Doulton T, He F, MacGregor G. MacGregor Angiotensin Receptor Blockade in Hypertension. Systematic Review of Combined Angiotensin-Converting Enzyme Inhibition and Angiotensin Receptor Blockade in Hypertension. Hypertension 2005; 45: 880–6.
15. Eklind-Cervenka M, Benson L, Dahlstrom U et al. Association of candesartan vs losartan with all-cause mortality in patients with heart failure. JAMA 2011; 305: 175.
16. Escobar C, Barrios V, Calderon A et al. Electrocardiographic left ventricular hypertrophy regression induced by an angiotensin receptor blocker-based regimen in hypertensive patients with the metabolic syndrome: data from the SARA Study. J Clin Hypertens (Greenwich) 2008; 10: 208–14.
17. Gleiter CH, Mörike KE. Clinical pharmacokinetics of candesartan. Clin Pharmacokinet 2002; 41 (1): 7–17.
18. Granger CB, McMurray JJ, Yusuf S et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003; 362: 772.
19. Inada Y, Ojima M, Kanagawa R et al. Pharmacologic properties of candesartan cilexetil – possible mechanisms of long-term antihypertensive action. J Hum Hypertens 1999; 13 (Suppl. 1): S75–S80.
20. Ishii H, Tsukada T, Yoshida M. Angiotensin II Type-I Receptor Blocker, Candesartan, Improves Brachial-Ankle Pulse Wave Velocity Independent of Its Blood Pressure Lowering Effects in Type 2 Diabetes Patients. J Soc Int Med 2008; 47: 2013–8.
21. Izuhara Y, Sada T, Yanagisawa H et al. A novel Sartan derivative with very low angiotensin II type 1 receptor affinity protects the kidney in type 2 diabetic rats. Arterioscler Thromb Vasc Biol 2008; 28 (10): 1767–73.
22. Lee HY, Hong BK, Chung WJ et al. Phase IV, 8-week, multicenter, randomized, active treatment-controlled, parallel group, efficacy, and tolerability study of high-dose candesartan cilexetil combined with hydrochlorothiazide in Korean adults with stage II hypertension. Clin Ther 2011; 33 (8): 1043–56.
23. Lee VC, Rhew DC, Dylan M et al. Meta-analysis: angiotensinreceptor blockers in chronic heart failure and high-risk acute myocardial infarction. Ann Intern Med 2004; 141: 693.
24. Linger T. Differences among angiotensin II type 1 receptor blockers: characterization of candesartan cilexetil. Blood Pressure 2000; 9 (Suppl. 1): 14–8.
25. Lithell H, Hansson L, Skoog I et al. SCOPE Study Group. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003; 21: 875–86.
26. McClellan KJ, Goa KL. Candesartan cilexetil. A review of its use in essential hypertension. Drugs 1998; 56: 847–69.
27. Minatoguchi S, Aoyama T, Kawai N et al. Comparative effect of candesartan and amlodipine, and effect of switching from valsartan, losartan, telmisartan and olmesartan to candesartan, on early morning hypertension and heart rate. Blood Press 2013; 22 (Suppl. 1): 29–37.
28. Miura S, Karnik S, Saku K. Review: Angiotensin II type 1 receptor blockers: class effects versus molecular effects. J Renin-Angiotensin-Aldosterone Syst 2011; 12: 1.
29. Ogihara T, Fujimoto A, Nakao K, Saruta T. CASE-J Trial Group. ARB candesartan and CCB amlodipine in hypertensive patients: the CASE-J trial. Exp Rev Cardiovasc Ther 2008; p. 1195–201.
30. Penicka M, Gregor P, Kerekes R et al. Candesartan use in Hypertrophic And Non-obstructive Cardiomyopathy Estate (CHANCE) Study. The effects of candesartan on left ventricular hypertrophy and function in nonobstructive hypertrophic cardiomyopathy: a pilot, randomized study. J Mol Diagn 2009; 11: 35–41.
31. Philipp T, Martinez F, Geiger H et al. Candesartan improves blood pressure control and reduces proteinuria in renal transplant recipients: results from SECRET. Nephrol Dial Transplant 2010; 25 (3): 967–76.
32. Sakamoto M, Suzuki H, Hayashi T et al. Effects of candesartan in hypertensive patients with type 2 diabetes mellitus on inflammatory parameters and their relationship to pulse pressure. Cardiovasc Diabetol 2012; 11: 118–23.
33. Saxby BK, Harrington F, Wesnes KA et al. Candesartan and cognitive decline in older patients with hypertension: a substudy of the SCOPE trial. Neurology 2008; 70 (19 Pt. 2): 1858–66.
34. Shimizu M, Ishikawa J, Yano Y et al. Association between asleep blood pressure and brain natriuretic peptide during antihypertensive treatment: the Japan Morning Surge-Target Organ Protection (J-TOP) study. J Hypertens 2012; 30 (5): 1015–21.
35. Tillin T, Orchard T, Malm A et al. The role of antihypertensive therapy in reducing vascular complications of type 2 diabetes. Findings from the DIabetic REtinopathy Candesartan Trials-Protect 2 study. J Hypertens 2011; 29 (7): 1457–62.
36. Van Liefde I, Vauquelin G. Sartan-AT1 receptor interactions: In vitro evidence for insurmountable antagonism and inverse agonism. Mol Cell Endocrinol 2009; 302: 237–43.
37. Weisser B, Gerwe M, Braun M, Funken C. Investigations of the antihypertensive long-term action of candesartan cilexetil in different dosages under the influence of therapy-free intervals Arzneimittelforschung 2005; 55 (9): 505–13.
38. Westerink J, Visseren F. Cardiovasc Pharmacological and nonpharmacological interventions to influence adipose tissue function. Cardiovasc Diabetol 2011; 10: 13.
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1. Evdokimova A.G., Lozhkina M.V., Kovalenko E.V. Evdokimov V.V. Klinicheskaia effektivnost' irbesartana u patsientov s serdechno-sosudistymi zabolevaniiami. Serdtse. 2012; 11 (6): 364–8. [in Russian]
2. Evdokimova A.G., Lozhkina M.V., Kovalenko E.V. Osobennosti primeneniia kandesartana v klinicheskoi praktike. Consilium Medicum. 2016; 18 (1): 54–9. [in Russian]
3. Giliarevskii S.R., Golshmid M.V., Kuz'mina I.M. Dokazatel'naia istoriia kandesartana: proshloe, budushchee i nastoiashchee. Serdechnaia nedostatochnost'. 2015; 16 (5): 303–10. [in Russian]
4. Rakov A.A., Khokhlov A.L., Fedorov V.N. i dr. Farmakoepidemiologiia khronicheskoi serdechnoi nedostatochnosti u ambulatornykh bol'nykh. Kachestvennaia klinicheskaia praktika. 2003; 2: 40–3. [in Russian]
5. Sirenko Iu.N., Donchenko N.V. Mesto kandesartana v sovremennoi terapii serdechno-sosudistykh zabolevanii: obzor dokazatel'stv. Arterial'naia gipertenziia. 2011; 4 (18): 114–26. [in Russian]
6. Khokhlov A.L., Sirotkina A.M., Mogutova I.S. i dr. Rasprostranennost' nekotorykh polimorfnykh variantov genov u bol'nykh s arterial'noi gipertenziei (materialy konferentsii “Kardiovaskuliarnaia profilaktika i reabilitatsiia 2013”, g. Moskva). Kardiovaskuliarnaia terapiia i profilaktika. 2013; 12: 41. [in Russian]
7. Shunikova M.I., Khokhlov A.L., Sosnin A.Iu. Sravnitel'naia otsenka organoprotektivnykh svoistv fozinoprila, amlodipina i metoprolola u bol'nykh arterial'noi gipertoniei. Consilium Medicum. 2008; 10 (11): 30–5. [in Russian]
8. Abrahamsson Т, Karp L, Brabdl-Eliasson II el al. Candesartan causes long-last antagonism of angiotensin II receptor-mediated contractile effects in isolated vascular preparations: a comparison with irbesartan, losartan and its active metabolite (EXP-3174). Blood Pressure 2000; 9 (Abstr. Suppl.): 1–52.
9. Azilsartan medoxomil (Edarbi) the eighth ARB. Med Lett Drugs Ther 2011; 16 (53): 1364.
10. Bangalore S. Angiotensin receptor blockers and risk of myocardial infarction: meta-analyses and trial sequential analyses of 147 020 patients from randomised trials. BMJ 2011; 342: d2234.
11. Brunner HR, Gavras H, Laragh JH et al. Angiotensin-II blockade in man by Sar1-Ala8-angiotensin II for understanding and treatment of high blood pressure. Lancet 1973; 2: 1045.
12. Cuspidi C, Muiesan ML, Valagussa L еt al. Comparative effects of candesartan and enalapril on left ventricular hypertrophy in patients with essential hypertension: the candesartan assessment in the treatment of cardiac hypertrophy (CATCH) study. J Hypertens 2002; 20: 2293–300.
13. De Rosa ML, Chiariello M. Candesartan improves maximal exercise capacity in hypertensives: results of a randomized placebo-controlled crossover trial. J Clin Hypertens (Greenwich) 2009; 11 (4): 192–200.
14. Doulton T, He F, MacGregor G. MacGregor Angiotensin Receptor Blockade in Hypertension. Systematic Review of Combined Angiotensin-Converting Enzyme Inhibition and Angiotensin Receptor Blockade in Hypertension. Hypertension 2005; 45: 880–6.
15. Eklind-Cervenka M, Benson L, Dahlstrom U et al. Association of candesartan vs losartan with all-cause mortality in patients with heart failure. JAMA 2011; 305: 175.
16. Escobar C, Barrios V, Calderon A et al. Electrocardiographic left ventricular hypertrophy regression induced by an angiotensin receptor blocker-based regimen in hypertensive patients with the metabolic syndrome: data from the SARA Study. J Clin Hypertens (Greenwich) 2008; 10: 208–14.
17. Gleiter CH, Mörike KE. Clinical pharmacokinetics of candesartan. Clin Pharmacokinet 2002; 41 (1): 7–17.
18. Granger CB, McMurray JJ, Yusuf S et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003; 362: 772.
19. Inada Y, Ojima M, Kanagawa R et al. Pharmacologic properties of candesartan cilexetil – possible mechanisms of long-term antihypertensive action. J Hum Hypertens 1999; 13 (Suppl. 1): S75–S80.
20. Ishii H, Tsukada T, Yoshida M. Angiotensin II Type-I Receptor Blocker, Candesartan, Improves Brachial-Ankle Pulse Wave Velocity Independent of Its Blood Pressure Lowering Effects in Type 2 Diabetes Patients. J Soc Int Med 2008; 47: 2013–8.
21. Izuhara Y, Sada T, Yanagisawa H et al. A novel Sartan derivative with very low angiotensin II type 1 receptor affinity protects the kidney in type 2 diabetic rats. Arterioscler Thromb Vasc Biol 2008; 28 (10): 1767–73.
22. Lee HY, Hong BK, Chung WJ et al. Phase IV, 8-week, multicenter, randomized, active treatment-controlled, parallel group, efficacy, and tolerability study of high-dose candesartan cilexetil combined with hydrochlorothiazide in Korean adults with stage II hypertension. Clin Ther 2011; 33 (8): 1043–56.
23. Lee VC, Rhew DC, Dylan M et al. Meta-analysis: angiotensinreceptor blockers in chronic heart failure and high-risk acute myocardial infarction. Ann Intern Med 2004; 141: 693.
24. Linger T. Differences among angiotensin II type 1 receptor blockers: characterization of candesartan cilexetil. Blood Pressure 2000; 9 (Suppl. 1): 14–8.
25. Lithell H, Hansson L, Skoog I et al. SCOPE Study Group. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003; 21: 875–86.
26. McClellan KJ, Goa KL. Candesartan cilexetil. A review of its use in essential hypertension. Drugs 1998; 56: 847–69.
27. Minatoguchi S, Aoyama T, Kawai N et al. Comparative effect of candesartan and amlodipine, and effect of switching from valsartan, losartan, telmisartan and olmesartan to candesartan, on early morning hypertension and heart rate. Blood Press 2013; 22 (Suppl. 1): 29–37.
28. Miura S, Karnik S, Saku K. Review: Angiotensin II type 1 receptor blockers: class effects versus molecular effects. J Renin-Angiotensin-Aldosterone Syst 2011; 12: 1.
29. Ogihara T, Fujimoto A, Nakao K, Saruta T. CASE-J Trial Group. ARB candesartan and CCB amlodipine in hypertensive patients: the CASE-J trial. Exp Rev Cardiovasc Ther 2008; p. 1195–201.
30. Penicka M, Gregor P, Kerekes R et al. Candesartan use in Hypertrophic And Non-obstructive Cardiomyopathy Estate (CHANCE) Study. The effects of candesartan on left ventricular hypertrophy and function in nonobstructive hypertrophic cardiomyopathy: a pilot, randomized study. J Mol Diagn 2009; 11: 35–41.
31. Philipp T, Martinez F, Geiger H et al. Candesartan improves blood pressure control and reduces proteinuria in renal transplant recipients: results from SECRET. Nephrol Dial Transplant 2010; 25 (3): 967–76.
32. Sakamoto M, Suzuki H, Hayashi T et al. Effects of candesartan in hypertensive patients with type 2 diabetes mellitus on inflammatory parameters and their relationship to pulse pressure. Cardiovasc Diabetol 2012; 11: 118–23.
33. Saxby BK, Harrington F, Wesnes KA et al. Candesartan and cognitive decline in older patients with hypertension: a substudy of the SCOPE trial. Neurology 2008; 70 (19 Pt. 2): 1858–66.
34. Shimizu M, Ishikawa J, Yano Y et al. Association between asleep blood pressure and brain natriuretic peptide during antihypertensive treatment: the Japan Morning Surge-Target Organ Protection (J-TOP) study. J Hypertens 2012; 30 (5): 1015–21.
35. Tillin T, Orchard T, Malm A et al. The role of antihypertensive therapy in reducing vascular complications of type 2 diabetes. Findings from the DIabetic REtinopathy Candesartan Trials-Protect 2 study. J Hypertens 2011; 29 (7): 1457–62.
36. Van Liefde I, Vauquelin G. Sartan-AT1 receptor interactions: In vitro evidence for insurmountable antagonism and inverse agonism. Mol Cell Endocrinol 2009; 302: 237–43.
37. Weisser B, Gerwe M, Braun M, Funken C. Investigations of the antihypertensive long-term action of candesartan cilexetil in different dosages under the influence of therapy-free intervals Arzneimittelforschung 2005; 55 (9): 505–13.
38. Westerink J, Visseren F. Cardiovasc Pharmacological and nonpharmacological interventions to influence adipose tissue function. Cardiovasc Diabetol 2011; 10: 13.
Авторы
Ю.В.Рыбачкова
ГБОУ ВПО Ярославский государственный медицинский университет Минздрава России. 150000, Россия, Ярославль, ул. Революционная, д. 5 julia3111@mail.ru
________________________________________________
Yu.V.Rybachkova
Yaroslavl State Medical University of the Ministry of Health of the Russian Federation. 150000, Russian Federation, Yaroslavl, ul. Revoliutsionnaia, d. 5 julia3111@mail.ru