systhiperСистемные гипертензииSystemic Hypertension2075-082X2542-2189LLC «ИнтерМедсервис»10.26442/2075082X.2019.3.190467systhiper-590Research ArticleСТАТЬИARTICLESВозможности блокатора рецепторов к ангиотензину азилсартана медоксомила и его комбинации с хлорталидоном в снижении сердечно-сосудистого риска у пациентов с ожирением, метаболическим синдромом и сахарным диабетомThe possibilities of angiotensin receptor blocker azilsartan medoxomil and its combination with chlortalidone in cardiovascular risk decrease in patients with obesity, metabolic syndrome and diabetes mellitushttps://orcid.org/0000-0001-7895-9068ЖернаковаЮ. В.ZhernakovaJ. V.juli001@mail.ruhttps://orcid.org/0000-0002-9822-4357ЧазоваИ. Е.ChazovaI. E.c34h@yandex.ruhttps://orcid.org/0000-0001-5215-4894БлиноваН. В.BlinovaN. V.nat-cardio1@yandex.ruФГБУ «НМИЦ кардиологии»РоссияNational Medical Research Center for CardiologyRussian Federation2019231220221633642Copyright © Жернакова Ю.В., Чазова И.Е., Блинова Н.В., 20222022Жернакова Ю.В., Чазова И.Е., Блинова Н.В.Zhernakova J.V., Chazova I.E., Blinova N.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.syst-hypertension.ru/jour/article/view/590

Для лечения артериальной гипертонии все чаще применяются блокаторы рецепторов к ангиотензину (БРА), особенно актуален этот класс препаратов у пациентов с ожирением, метаболическим синдромом и сахарным диабетом. Однако не все БРА могут стать препаратами первого выбора у этой категории пациентов. К антигипертензивным препаратам для больных артериальной гипертонией с метаболическими нарушениями предъявляются особые требования - высокая антигипертензивная эффективность, максимальная продолжительность действия, возможность улучшать чувствительность периферических тканей к инсулину и, соответственно, метаболический профиль. Кроме того, данная категория пациентов нуждается в комбинированной терапии уже на старте лечения. Комбинаций БРА, обладающих всеми этими свойствами, с тиазидоподобными диуретиками крайне мало. Настоящий обзор посвящен возможностям нового БРА азилсартана медоксомила (Эдарби®) и его комбинации с хлорталидоном (Эдарби® Кло) в снижении сердечно-сосудистого риска у пациентов с ожирением, метаболическим синдромом и сахарным диабетом.

Angiotensin receptor blockers (ARBs) are with increasing frequency used in arterial hypertension treatment, this class of medications is especially important in treatment of patients with obesity, metabolic syndrome and diabetes mellitus. Although not all the ARBs are the therapy of first choice in these patients. The special requirements are imposed upon antihypertensive mediations for patients with arterial hypertension and metabolic disorders such as high antihypertensive activity, maximum duration of action, possibility of increase of peripheral tissues sensitivity to insulin and, subsequently, metabolic profile. Besides, these patients require the use of combined therapy already at the treatment start. There are very few ARBs combinations with thiazide diuretics that exhibit these properties. The present review discusses possibilities of new ARB azilsartan medoxomil (Edarbi®) and its combination with chlortalidone (Edarbi® Clo) in decrease of cardiovascular risk in patients with obesity, metabolic syndrome and diabetes mellitus.

артериальная гипертонияожирениеметаболический синдромсахарный диабетблокаторы рецепторов к ангиотензинухлорталидонантигипертензивная терапиякомбинированная терапиясердечно-сосудистый рискarterial hypertensionobesitymetabolic syndromediabetes mellitusangiotensin receptor blockerschlortalidoneantihypertensive treatmentcombined therapycardiovascular riskReferencesEmdin C.A, Rahimi K, Neal B et al. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA 2015; 313: 603-15.Emdin C.A, Rahimi K, Neal B et al. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA 2015; 313: 603-15.Ettehad D, Emdin C.A, Kiran A et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 2016; 387: 957-67.Ettehad D, Emdin C.A, Kiran A et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 2016; 387: 957-67.Forouzanfar M.H, Liu P, Roth G.A et al. Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 1990-2015. JAMA 2017; 317: 165-82.Forouzanfar M.H, Liu P, Roth G.A et al. Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 1990-2015. JAMA 2017; 317: 165-82.Lewington S, Clarke R, Qizilbash N et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903-13.Lewington S, Clarke R, Qizilbash N et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903-13.NCD Risk Factor Collaboration. Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants. Lancet 2017; 389: 37-55.NCD Risk Factor Collaboration. Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants. Lancet 2017; 389: 37-55.O’Donnell M.J, Chin S.L, Rangarajan S et al. INTERSTROKE Investigators. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. Lancet 2016; 388: 761-75.O’Donnell M.J, Chin S.L, Rangarajan S et al. INTERSTROKE Investigators. Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study. Lancet 2016; 388: 761-75.Rapsomaniki E, Timmis A, George J et al. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1.25 million people. Lancet 2014; 383: 1899-911.Rapsomaniki E, Timmis A, George J et al. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1.25 million people. Lancet 2014; 383: 1899-911.Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension. 1. Overview, meta-analyses, and metaregression analyses of randomized trials. J Hypertens 2014; 32: 2285-95.Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension. 1. Overview, meta-analyses, and metaregression analyses of randomized trials. J Hypertens 2014; 32: 2285-95.Tsai W.C, Wu H.Y, Peng Y.S et al. Association of intensive blood pressure control and kidney disease progression in nondiabetic patients with chronic kidney disease: a systematic review and meta-analysis. JAMA Intern Med 2017; 177: 792-9.Tsai W.C, Wu H.Y, Peng Y.S et al. Association of intensive blood pressure control and kidney disease progression in nondiabetic patients with chronic kidney disease: a systematic review and meta-analysis. JAMA Intern Med 2017; 177: 792-9.Yusuf S, Hawken S, Ounpuu S et al.; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364: 937-52.Yusuf S, Hawken S, Ounpuu S et al.; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364: 937-52.Banegas J.R, Lopez-Garcia E, Dallongeville J et al. Achievement of treatment goals for primary prevention of cardiovascular disease in clinical practice across Europe: the EURIKA study. Eur Heart J 2011; 32: 2143-52.Banegas J.R, Lopez-Garcia E, Dallongeville J et al. Achievement of treatment goals for primary prevention of cardiovascular disease in clinical practice across Europe: the EURIKA study. Eur Heart J 2011; 32: 2143-52.Chow C.K, Teo K.K, Rangarajan S et al; PURE Study Investigators. Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries. JAMA 2013; 310: 959-68.Chow C.K, Teo K.K, Rangarajan S et al; PURE Study Investigators. Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries. JAMA 2013; 310: 959-68.Falaschetti E, Mindell J, Knott C, Poulter N. Hypertension management in England: a serial cross-sectional study from 1994 to 2011. Lancet 2014; 383: 1912-9.Falaschetti E, Mindell J, Knott C, Poulter N. Hypertension management in England: a serial cross-sectional study from 1994 to 2011. Lancet 2014; 383: 1912-9.Tocci G, Rosei E.A, Ambrosioni E et al. Blood pressure control in Italy: analysis of clinical data from 2005-2011 surveys on hypertension. J Hypertens 2012; 30: 1065-74.Tocci G, Rosei E.A, Ambrosioni E et al. Blood pressure control in Italy: analysis of clinical data from 2005-2011 surveys on hypertension. J Hypertens 2012; 30: 1065-74.Finucane M.M et al. National, regional, and global trends in body mass index since 1980: Systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet Lond Engl 2011; 377 (9765): 557-67.Finucane M.M et al. National, regional, and global trends in body mass index since 1980: Systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet Lond Engl 2011; 377 (9765): 557-67.Caleyachetty R et al. Metabolically Healthy Obese and Incident Cardiovascular Disease Events Among 3.5 Million Men and Women. J Am Coll Cardiol 2017; 70 (12): 1429-37.Caleyachetty R et al. Metabolically Healthy Obese and Incident Cardiovascular Disease Events Among 3.5 Million Men and Women. J Am Coll Cardiol 2017; 70 (12): 1429-37.Guh D.P, Zhang W, Bansback N et al. The incidence of co-morbidities related to obesity and overweight: A systematic review and meta-analysis. BMC Public Health 2009; 9 (88).Guh D.P, Zhang W, Bansback N et al. The incidence of co-morbidities related to obesity and overweight: A systematic review and meta-analysis. BMC Public Health 2009; 9 (88).Anari R, Amani R, Latifi S.M et al. Association of obesity with hypertension and dyslipidemia in type 2 diabetes mellitus subjects. Diabetes Metab Syndr Clin Res. Rev 2017; 11 (1): 37-41.Anari R, Amani R, Latifi S.M et al. Association of obesity with hypertension and dyslipidemia in type 2 diabetes mellitus subjects. Diabetes Metab Syndr Clin Res. Rev 2017; 11 (1): 37-41.Wilson P.W.F, D’Agostino R.B, Sullivan L et al. Overweight and Obesity as Determinants of Cardiovascular Risk: The Framingham Experience. Arch Intern Med 2002; 162 (16): 1867-72.Wilson P.W.F, D’Agostino R.B, Sullivan L et al. Overweight and Obesity as Determinants of Cardiovascular Risk: The Framingham Experience. Arch Intern Med 2002; 162 (16): 1867-72.Mancusi C et al. Differential effect of obesity on prevalence of cardiac and carotid target organ damage in hypertension (the Campania Salute Network). Int J Cardiol 2017; 244: 260-4.Mancusi C et al. Differential effect of obesity on prevalence of cardiac and carotid target organ damage in hypertension (the Campania Salute Network). Int J Cardiol 2017; 244: 260-4.Ohnishi H et al. Incidence of Hypertension in Individuals with Abdominal Obesity in a Rural Japanese Population: The Tanno and Sobetsu Study. Hypertens Res 2008; 31 (7): 1385-90.Ohnishi H et al. Incidence of Hypertension in Individuals with Abdominal Obesity in a Rural Japanese Population: The Tanno and Sobetsu Study. Hypertens Res 2008; 31 (7): 1385-90.Jahangir E, Schutter ADe, Lavie C.J. The relationship between obesity and coronary artery disease. Transl Res 2014; 164 (4): 336-44.Jahangir E, Schutter ADe, Lavie C.J. The relationship between obesity and coronary artery disease. Transl Res 2014; 164 (4): 336-44.Despres J.P, Moorjani S, Lupien P.J et al. Regional distribution of body fat, plasma insulin, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis 1990; 10: 497-511.Despres J.P, Moorjani S, Lupien P.J et al. Regional distribution of body fat, plasma insulin, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis 1990; 10: 497-511.Fox C.S, Massaro J.M, Hoffmann U et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 2007; 116: 39-48.Fox C.S, Massaro J.M, Hoffmann U et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 2007; 116: 39-48.Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998; 317: 703-13.Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998; 317: 703-13.Tatti P, Pahor M, Byington R.P et al. Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM. Diabetes Care 1998; 21: 597-603.Tatti P, Pahor M, Byington R.P et al. Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM. Diabetes Care 1998; 21: 597-603.Estacio R.O, Jeffers B.W, Hiatt W.R et al. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. N Engl J Med 1998; 338: 645-52.Estacio R.O, Jeffers B.W, Hiatt W.R et al. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. N Engl J Med 1998; 338: 645-52.Niskanen L, Hedner T, Hansson L et al. Reduced cardiovascular morbidity and mortality in hypertensive diabetic patients on first-line therapy with an ACE inhibitor compared with a diuretic/beta-blocker-based treatment regimen: a subanalysis of the Captopril Prevention Project. Diabetes Care 2001; 24: 2091-6.Niskanen L, Hedner T, Hansson L et al. Reduced cardiovascular morbidity and mortality in hypertensive diabetic patients on first-line therapy with an ACE inhibitor compared with a diuretic/beta-blocker-based treatment regimen: a subanalysis of the Captopril Prevention Project. Diabetes Care 2001; 24: 2091-6.Lindholm L.H, Hansson L, Ekbom T et al. Comparison of antihypertensive treatments in preventing cardiovascular events in elderly diabetic patients: results from the Swedish Trial in Old Patients with Hypertension-2. STOP Hypertension-2 Study Group. J Hypertens 2000; 18: 1671-5.Lindholm L.H, Hansson L, Ekbom T et al. Comparison of antihypertensive treatments in preventing cardiovascular events in elderly diabetic patients: results from the Swedish Trial in Old Patients with Hypertension-2. STOP Hypertension-2 Study Group. J Hypertens 2000; 18: 1671-5.Thomopoulosa C, Parati G, Zanchetti A. Effects of blood-pressure-lowering treatment on outcome incidence in hypertension: Should blood pressure management differ in hypertensive patients with and without diabetes mellitus? Overview and meta-analyses of randomized trials. J Hypertension 2017, 35: 922-44.Thomopoulosa C, Parati G, Zanchetti A. Effects of blood-pressure-lowering treatment on outcome incidence in hypertension: Should blood pressure management differ in hypertensive patients with and without diabetes mellitus? Overview and meta-analyses of randomized trials. J Hypertension 2017, 35: 922-44.Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension. Head-to-head comparisons of various classes of antihypertensive drugs. Overview and meta-analyses. J Hypertens 2015; 33: 1321-41.Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension. Head-to-head comparisons of various classes of antihypertensive drugs. Overview and meta-analyses. J Hypertens 2015; 33: 1321-41.Elliott W.J, Meyer P.M. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet 2007; 369 (9557): 201-7.Elliott W.J, Meyer P.M. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet 2007; 369 (9557): 201-7.Edarbi® (azilsartan medoxomil) prescribing information. Takeda Pharmaceuticals America, Inc., 2012. Data on file. Takeda Pharmaceutical Company Limited.Edarbi® (azilsartan medoxomil) prescribing information. Takeda Pharmaceuticals America, Inc., 2012. Data on file. Takeda Pharmaceutical Company Limited.Bönner G et al. Comparison of antihypertensive efficacy of the new angiotensin receptor blocker azilsartan medoxomil with ramipril. J Hypertens 2010; 28: e283.Bönner G et al. Comparison of antihypertensive efficacy of the new angiotensin receptor blocker azilsartan medoxomil with ramipril. J Hypertens 2010; 28: e283.White W.B et al. Effects of the angiotensin receptor blocker azilsartan medoxomil versus olmesartan and valsartan on ambulatory and clinic blood pressure in patients with stages 1 and 2 hypertension. Hypertension 2011; 57: 413-20.White W.B et al. Effects of the angiotensin receptor blocker azilsartan medoxomil versus olmesartan and valsartan on ambulatory and clinic blood pressure in patients with stages 1 and 2 hypertension. Hypertension 2011; 57: 413-20.Kusumoto K et al. Antihypertensive, insulin-sensitising and renoprotective effects of a novel, potent and long-acting angiotensin II type 1 receptor blocker, azilsartan medoxomil, in rat and dog models. Eur J Pharmacology 2011; 669: 84-93.Kusumoto K et al. Antihypertensive, insulin-sensitising and renoprotective effects of a novel, potent and long-acting angiotensin II type 1 receptor blocker, azilsartan medoxomil, in rat and dog models. Eur J Pharmacology 2011; 669: 84-93.Iwai M. TAK-536, a new receptor blocker, improved glucose intolerans and adipocyt differentiation. AJH 2007; 20: 579-86.Iwai M. TAK-536, a new receptor blocker, improved glucose intolerans and adipocyt differentiation. AJH 2007; 20: 579-86.Недогода С.В., Чумачек Е.В., Цома В.В. и др. Возможности азилсартана в коррекции инсулинорезистентности и уровня адипокинов при артериальной гипертензии в сравнении с другими сартанами. Рос. кардиол. журн. 2019; 24 (1): 1-9. @@Nedogoda S.V., Chumachek E.V., Tsoma V.V. et al. Vozmozhnosti azilsartana v korrektsii insulinorezistentnosti i urovnia adipokinov pri arterial'noi gipertenzii v sravnenii s drugimi sartanami. Ros. kardiol. zhurn. 2019; 24 (1): 1-9. (in Russian).]Недогода С.В., Чумачек Е.В., Цома В.В. и др. Возможности азилсартана в коррекции инсулинорезистентности и уровня адипокинов при артериальной гипертензии в сравнении с другими сартанами. Рос. кардиол. журн. 2019; 24 (1): 1-9. @@Nedogoda S.V., Chumachek E.V., Tsoma V.V. et al. Vozmozhnosti azilsartana v korrektsii insulinorezistentnosti i urovnia adipokinov pri arterial'noi gipertenzii v sravnenii s drugimi sartanami. Ros. kardiol. zhurn. 2019; 24 (1): 1-9. (in Russian).]Чазова И.Е., Жернакова Ю.В., Блинова Н.В., Рогоза А.Н. Новый блокатор рецепторов к ангиотензину II Эдарби®, как часть патогенетического лечения артериальной гипертонии у больных с метаболическими нарушениями. Системные гипертензии. 2017; 14 (3): 28-35. DOI: 10.26442/2075-082X_14.3.28-35 @@Chazova I.E., Zhernakova Yu.V., Blinova N.V., Rogoza A.N. Novyi blokator retseptorov k angiotenzinu II Edarbi®, kak chast' patogeneticheskogo lecheniia arterial'noi gipertonii u bol'nykh s metabolicheskimi narusheniiami. Systemic Hypertension. 2017; 14 (3): 28-35. DOI: 10.26442/2075-082X_14.3.28-35 (in Russian).]Чазова И.Е., Жернакова Ю.В., Блинова Н.В., Рогоза А.Н. Новый блокатор рецепторов к ангиотензину II Эдарби®, как часть патогенетического лечения артериальной гипертонии у больных с метаболическими нарушениями. Системные гипертензии. 2017; 14 (3): 28-35. DOI: 10.26442/2075-082X_14.3.28-35 @@Chazova I.E., Zhernakova Yu.V., Blinova N.V., Rogoza A.N. Novyi blokator retseptorov k angiotenzinu II Edarbi®, kak chast' patogeneticheskogo lecheniia arterial'noi gipertonii u bol'nykh s metabolicheskimi narusheniiami. Systemic Hypertension. 2017; 14 (3): 28-35. DOI: 10.26442/2075-082X_14.3.28-35 (in Russian).]Williams B, Mancia G, Spiering W et al; ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018; 39 (33): 3021-104.Williams B, Mancia G, Spiering W et al; ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018; 39 (33): 3021-104.Чазова И.Е., Жернакова Ю.В. от имени экспертов. Клинические рекомендации. Диагностика и лечение артериальной гипертонии. Системные гипертензии. 2019; 16 (1): 6-31. @@Chazova I.E., Zhernakova Yu.V. ot imeni ekspertov. Klinicheskie rekomendatsii. Diagnostika i lechenie arterial'noi gipertonii. Systemic Hypertension. 2019; 16 (1): 6-31. DOI: 10.26442/2075082X.2019.1.190179 (in Russian).]Чазова И.Е., Жернакова Ю.В. от имени экспертов. Клинические рекомендации. Диагностика и лечение артериальной гипертонии. Системные гипертензии. 2019; 16 (1): 6-31. @@Chazova I.E., Zhernakova Yu.V. ot imeni ekspertov. Klinicheskie rekomendatsii. Diagnostika i lechenie arterial'noi gipertonii. Systemic Hypertension. 2019; 16 (1): 6-31. DOI: 10.26442/2075082X.2019.1.190179 (in Russian).]Gradman A.H, Parisé H, Lefebvre P et al. Initial combination therapy reduces the risk of cardiovascular events in hypertensive patients: a matched cohort study. Hypertension 2013; 61: 309-18.Gradman A.H, Parisé H, Lefebvre P et al. Initial combination therapy reduces the risk of cardiovascular events in hypertensive patients: a matched cohort study. Hypertension 2013; 61: 309-18.Arnett D.K, Blumenthal R.S, Albert M.A et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019. DOI: 10.1161/CIR.0000000000000678Arnett D.K, Blumenthal R.S, Albert M.A et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019. DOI: 10.1161/CIR.0000000000000678ALLHAT Officers and Coordinators; ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288 (23): 2981-97.ALLHAT Officers and Coordinators; ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288 (23): 2981-97.Mortality after 10 1/2 years for hypertensive participants in the Multiple Risk Factor Intervention Trial. Circulation 1990; 82 (5): 1616-28.Mortality after 10 1/2 years for hypertensive participants in the Multiple Risk Factor Intervention Trial. Circulation 1990; 82 (5): 1616-28.Кurtz T.W. Chlorthalidone: don’t call it “thiazide-like” anymore. Hypertension 2010; 56: 335-7.Кurtz T.W. Chlorthalidone: don’t call it “thiazide-like” anymore. Hypertension 2010; 56: 335-7.Carter B.L, Ernst M.E, Cohen J.D. Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability. Hypertension 2004; 43: 4-9.Carter B.L, Ernst M.E, Cohen J.D. Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability. Hypertension 2004; 43: 4-9.George L. Bakris, M.D, Domenic Sica et al. Antihypertensive Efficacy of Hydrochlorothiazide vs Chlorthalidone Combined with Azilsartan Medoxomil. Am J Med 2012; 125 (12): 1229.e1-1229.e10George L. Bakris, M.D, Domenic Sica et al. Antihypertensive Efficacy of Hydrochlorothiazide vs Chlorthalidone Combined with Azilsartan Medoxomil. Am J Med 2012; 125 (12): 1229.e1-1229.e10Cushman W.C, Bakris G.L et al. Azilsartan Medoxomil Plus Chlorthalidone Reduces Blood Pressure More Effectively Than Olmesartan Plus Hydrochlorothiazide in Stage 2 Systolic Hypertension. Hypertension 2012; 60: 310-8.Cushman W.C, Bakris G.L et al. Azilsartan Medoxomil Plus Chlorthalidone Reduces Blood Pressure More Effectively Than Olmesartan Plus Hydrochlorothiazide in Stage 2 Systolic Hypertension. Hypertension 2012; 60: 310-8.

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