cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLC10.15829/1728-8800-2018-6-86-94cardiovascular-2188Research ArticleОБЗОРЫREVIEWSФиксированные комбинации в современных алгоритмах лечения артериальной гипертензииFixed combinations in modern hypertension treatment algorithmshttps://orcid.org/0000-0001-9611-5096СаютинаЕ. В.SayutinaE. V.

Саютина Елена Витальевна — кандидат медицинских наук, ассистент кафедры поликлинической терапии.

Тел.: +7 (963) 695-14-05

493400@gmail.comФГАОУ ВО Первый Московский государственный медицинский университет имени И. М. Сеченова Минздрава России (Сеченовский Университет)I.M. Sechenov First Moscow State Medical University2018201220181768694Copyright © Саютина Е.В., 20182018Саютина Е.В.Sayutina E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/2188

Современное адекватное лечение артериальной гипертензии предусматривает использование комбинированной антигипертензивной терапии. В обновленной версии рекомендаций Европейского общества кардиологов 2018 блокаторы ренин-ангиотензин-альдо-стероновой системы укрепили свои позиции в качестве препаратов первой линии, в т.ч. в комбинации с гидрохлортиазидом. В настоящей статье представлены алгоритмы ведения больных с неосложненной и бессимптомной (при наличии поражения органов-мишеней) артериальной гипертензией, а также у пациентов с сопутствующей сердечно-сосудистой, цереброваскулярной, почечной патологией и сахарным диабетом, и место в этой терапии фиксированной комбинации кандесартан/гидрохлоротиазид. В статье представлены результаты исследований, которые подтвердили не только высокую антигипертензивную эффективность этой комбинации, но и продемонстрировали ее нейтральный метаболический профиль, органопротективные эффекты, возможность использования у пациентов с хронической болезнью почек, хронической сердечной недостаточностью, инсультом в анамнезе, а также хорошую переносимость и высокую приверженность лечению.

Modern appropriate treatment of hypertension involves the use of combination antihypertensive therapy. According to updated version of European Society of Cardiology 2018 guidelines, renin-angiotensin-aldosterone system blockers must be used as first-line drugs, including in combination with hydrochlorothiazide. This article presents the algorithms for the management of patients with uncomplicated and asymptomatic (with target lesions) arterial hypertension. It also described the management of patients with concomitant cardiovascular, cerebrovascular, renal pathology and diabetes mellitus, and use of fixed combination of candesartan and hydrochlorothiazide. The article presents research data that confirmed not only the high antihypertensive efficacy of this combination, but also demonstrated its neutral metabolic profile, organ-protective effects, the ability to use in patients with chronic kidney disease, chronic heart failure, prior stroke, as well as high tolerability and treatment adherence.

артериальная гипертензиятерапевтические алгоритмыкомбинированная антигипертензивная терапияфиксированные комбинациипоражение органов-мишенейблокаторы РААСкандесартантиазидные диуретикиarterial hypertensiontherapeutic algorithmscombined antihypertensive therapyfixed combinationstarget lesionsRAAS blockerscandesartanthiazide diuretics-ReferencesForouzanfar MH, Afshin A, Alexander LT, et al. Global, regional, and national comparative risk assessment of 79 behavioral, environmental and occupational, and metabolic risks or clusters of risks, 1990±2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388:1659-724. doi:10.1016/S0140-6736(16)31679-8.Forouzanfar MH, Afshin A, Alexander LT, et al. Global, regional, and national comparative risk assessment of 79 behavioral, environmental and occupational, and metabolic risks or clusters of risks, 1990±2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388:1659-724. doi:10.1016/S0140-6736(16)31679-8.Диагностика и лечение артериальной гипертензии. Российские рекомендации (четвертый пересмотр). Российское медицинское общество по артериальной гипертонии. Всероссийское научное общество кардиологов. Журнал Системные гипертензии. 2010;3:5-26.Diagnosis and treatment of arterial hypertension. National recommendations (fourth revision). Russian medical society on arterial hypertension. Russian scientific society of cardiology. Systemic hypertension. 2010;3:5-26. (In Russ)Gradman AH, Basile JN, Carter BL, Bakris GL. Combination therapy in hypertension. J Am Soc Hypertens. 2010;4:90-8. doi:10.1016/j.jash.2010.03.001.Gradman AH, Basile JN, Carter BL, Bakris GL. Combination therapy in hypertension. J Am Soc Hypertens. 2010;4:90-8. doi:10.1016/j.jash.2010.03.001.James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults. JAMA. 2014;311:507 doi:10.1001/jama.2013.284427.James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults. JAMA. 2014;311:507 doi:10.1001/jama.2013.284427.Leung AA, Daskalopoulou SS, Dasgupta K, et al. Hypertension Canada's 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults. Can J Cardiol. 2017;33:557-76. doi:10.1016/j.cjca.2017.03.005.Leung AA, Daskalopoulou SS, Dasgupta K, et al. Hypertension Canada's 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults. Can J Cardiol. 2017;33:557-76. doi:10.1016/j.cjca.2017.03.005.Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/ AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Hypertension. 2017; HYP.0000000000000065. doi:10.1161/HYP.0000000000000065.Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/ AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Hypertension. 2017; HYP.0000000000000065. doi:10.1161/HYP.0000000000000065.Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-104. doi:10.1093/eurheartj/ehy339.Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-104. doi:10.1093/eurheartj/ehy339.Диагностика и лечение артериальной гипертензии. Российские рекомендации 2008 г. (3-й пересмотр). Кардиоваскулярная терапия и профилактика. 2008;7(6). Приложение 2.Diagnosis and treatment of hypertension. Russian recommendations 2008 (3rd revision). Cardiovascular Therapy and Prevention. 2008;7(6). Suppl. 2. (In Russ)Guide of arterial hypertension. Ed.: Ye. I. Chazov, I. Ye. Chazova. M., 2005. pp. 65577. (In Russ) Руководство по артериальной гипертонии. Под ред. Е. И. Чазова, И. Е. Чазовой. М., 2005. сс. 655-77. ISBN 5-9900251-3-0.Guide of arterial hypertension. Ed.: Ye. I. Chazov, I. Ye. Chazova. M., 2005. pp. 65577. (In Russ) Руководство по артериальной гипертонии. Под ред. Е. И. Чазова, И. Е. Чазовой. М., 2005. сс. 655-77. ISBN 5-9900251-3-0.Dzau V, Sasamura H, Hein L, et al. Heterogenity of angiotensin synthetic pathways and receptor subtypes: physiological and pharmacological implications. J. Hypertens. 1993 ;11(3):11-8.Dzau V, Sasamura H, Hein L, et al. Heterogenity of angiotensin synthetic pathways and receptor subtypes: physiological and pharmacological implications. J. Hypertens. 1993 ;11(3):11-8.Burnier M. Pathophysiological and clinical implications of AT(1) and AT(2) angiotensin II receptors in essential hypertension. Drugs. 2002;62(1):21-9.Burnier M. Pathophysiological and clinical implications of AT(1) and AT(2) angiotensin II receptors in essential hypertension. Drugs. 2002;62(1):21-9.Law M, Wald N, Morris J. Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy. Health Technol Assess. 2003;7(31).Law M, Wald N, Morris J. Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy. Health Technol Assess. 2003;7(31).Reboldi G, Angeli F, Cavallini C. Comparison between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the risk of myocardial infarction, stroke and death: a meta-analysis. Hypertens. 2008;26:1282-9. doi: 10.1097/HJH.0b013e328306ebe2.Reboldi G, Angeli F, Cavallini C. Comparison between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the risk of myocardial infarction, stroke and death: a meta-analysis. Hypertens. 2008;26:1282-9. doi: 10.1097/HJH.0b013e328306ebe2.Schrader J, Luders S, Kulschewski A. MOsEs study Group. Morbidity and mortality after stroke, epro- sartan compared with nitrendipine for secondary prevention: principal results of a prospective randomized controlled study (MOsEs). Stroke. 2005;36:1218-26.Schrader J, Luders S, Kulschewski A. MOsEs study Group. Morbidity and mortality after stroke, epro- sartan compared with nitrendipine for secondary prevention: principal results of a prospective randomized controlled study (MOsEs). Stroke. 2005;36:1218-26.Potier L, Roussel R, Elbez Y, et al. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in high vascular risk. Heart. 2017;103:1339-46. doi:10.1136/heartjnl-2016-310705.Potier L, Roussel R, Elbez Y, et al. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in high vascular risk. Heart. 2017;103:1339-46. doi:10.1136/heartjnl-2016-310705.Зырянов С. К., Бутранова О. И. Антигипертензивная терапия: от клинической фармакологии до клинического результата. Или что важно знать, выбирая антигипертензивный препарат. Сердце: журнал для практикующих врачей. 2017;16(4):288-98. doi:10.18087/rhj.2017.4.2381.Zyryanov SK, Butranova OI. Antihypertensive therapy: from clinical pharmacology to clinical outcome. Or what is important to know when choosing an antihypertensive drug. Heart: a magazine for practitioners. 2017;16(4):288-98. (In Russ.) doi:10.18087/rhj.2017.4.2381.Ostroumova OD, Bondarets OV, Guseva TF. Advantages of candesartan in the treatment of arterial hypertension. Systemic hypertension. 2014;2:62-6. (In Russ.) Остроумова О. Д., Бондарец О. В., Гусева Т. Ф. Преимущества кандесартана в лечении артериальной гипертонии. Системные гипертензии. 2014;2:62-6.Ostroumova OD, Bondarets OV, Guseva TF. Advantages of candesartan in the treatment of arterial hypertension. Systemic hypertension. 2014;2:62-6. (In Russ.) Остроумова О. Д., Бондарец О. В., Гусева Т. Ф. Преимущества кандесартана в лечении артериальной гипертонии. Системные гипертензии. 2014;2:62-6.Minatoguchi Sh, 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 Pressure. 2013;22(Suppl 1):29-37 doi:10.3109/08037051.2013.757844.Minatoguchi Sh, 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 Pressure. 2013;22(Suppl 1):29-37 doi:10.3109/08037051.2013.757844.Hasegawa H, Takano H, Kameda Y, et al. Effect of Switching from Telmisartan, Valsartan, Olmesartan, or Losartan to Candesartan on Morning Hypertension. Clin Experim Hypertens. 2012;34(2):86-91. doi:10.3109/10641963.2011.628729.Hasegawa H, Takano H, Kameda Y, et al. Effect of Switching from Telmisartan, Valsartan, Olmesartan, or Losartan to Candesartan on Morning Hypertension. Clin Experim Hypertens. 2012;34(2):86-91. doi:10.3109/10641963.2011.628729.ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. 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;288:2981-97. doi:10.1001/jama.288.23.2981.ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. 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;288:2981-97. doi:10.1001/jama.288.23.2981.Brenner BM, Cooper ME, De Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. The RENAAL Study Investigation. N Engl J Med. 2001;345:861-9. doi:10.1056/NEJMoa011161.Brenner BM, Cooper ME, De Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. The RENAAL Study Investigation. N Engl J Med. 2001;345:861-9. doi:10.1056/NEJMoa011161.Guul SJ, Os I, Jounela AJ. The efficacy and tolerability of enalapril in a formulation with a very low dose of hydrochlorothiazide in hypertensive patients resistant to enalapril monotherapy. Am J Hypertens. 1995;8:727-31.Guul SJ, Os I, Jounela AJ. The efficacy and tolerability of enalapril in a formulation with a very low dose of hydrochlorothiazide in hypertensive patients resistant to enalapril monotherapy. Am J Hypertens. 1995;8:727-31.Koenig W. On behalf of the Multicenter Study Group. Comparison of the Efficacy and Tolerability of Combination Tablets Containing Candesartan Cilexetil and Hydrochlorothiazide or Losartan and Hydrochlorothiazide in Patients with Moderate to Severe Hypertension Results of the CARLOS-Study. Clin Drug Invest. 2000;19(4):239-46.Koenig W. On behalf of the Multicenter Study Group. Comparison of the Efficacy and Tolerability of Combination Tablets Containing Candesartan Cilexetil and Hydrochlorothiazide or Losartan and Hydrochlorothiazide in Patients with Moderate to Severe Hypertension Results of the CARLOS-Study. Clin Drug Invest. 2000;19(4):239-46.2013 ESH/ESC Guidelines for the management of arterial hypertension. J Hypertens. 2013;31:1281-357. doi:101097/01.hjh.0000431740.32696.cc.2013 ESH/ESC Guidelines for the management of arterial hypertension. J Hypertens. 2013;31:1281-357. doi:101097/01.hjh.0000431740.32696.cc.Подзолков В. И., Тарзиманова А. И. Фиксированные комбинации в лечении артериальной гипертензии: новые возможности. Российский кардиологический журнал. 2018;23(5):68-73. doi:10.15829/1560-4071-2018-5-68-73.Podzolkov VI, Tarzimanova AI. Fixed combinations in the treatment of arterial hypertension: new opportunities. Russian Journal of Cardiology. 2018;23(5):68-73. (In Russ.) doi:10.15829/1560-4071-2018-5-68-73.Bonner G, Fuchs W. Fixed combination of candesartan with hydrochlorothiazide in patients with severe primary hypertension. Curr Med Res Opin. 2004;20(5):597-602.Bonner G, Fuchs W. Fixed combination of candesartan with hydrochlorothiazide in patients with severe primary hypertension. Curr Med Res Opin. 2004;20(5):597-602.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.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.Ogihara T, Fujimoto A, Nakao K, Saruta T. CASE-J Trial Group. ARB candesartan and CCB amlodipine in hypertensive patients: the CASE-J trial. Expert Rev. Cardiovasc Ther. 2008:1195-201. doi:10.1586/14779072.6.9.1195.Ogihara T, Fujimoto A, Nakao K, Saruta T. CASE-J Trial Group. ARB candesartan and CCB amlodipine in hypertensive patients: the CASE-J trial. Expert Rev. Cardiovasc Ther. 2008:1195-201. doi:10.1586/14779072.6.9.1195.Kasanuki H, Hagiwara N, Hosoda S, et al., HIJCREATE Investigators. Angiotensin II receptor blockerbased vs. nonangiotensin II receptor blockerbased therapy in patients with angiographically documented coronary artery disease and hypertension: the Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease (HIJ-CREATE). Eur Heart J. 2009;30:1203-12. doi:10.1093/eurheartj/ehp101.Kasanuki H, Hagiwara N, Hosoda S, et al., HIJCREATE Investigators. Angiotensin II receptor blockerbased vs. nonangiotensin II receptor blockerbased therapy in patients with angiographically documented coronary artery disease and hypertension: the Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease (HIJ-CREATE). Eur Heart J. 2009;30:1203-12. doi:10.1093/eurheartj/ehp101.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. doi:10.1097/01.hjh.0000059028.82022.89.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. doi:10.1097/01.hjh.0000059028.82022.89.Drawz PE, Alper AB, Anderson AH, et al. Chronic Renal Insufficiency Cohort Study Investigators. Masked hypertension and elevated nighttime blood pressure in CKD: prevalence and association with target organ damage. Clin J Am Soc Nephrol. 2016;11:642-52. doi:10.2215/CJN.08530815.Drawz PE, Alper AB, Anderson AH, et al. Chronic Renal Insufficiency Cohort Study Investigators. Masked hypertension and elevated nighttime blood pressure in CKD: prevalence and association with target organ damage. Clin J Am Soc Nephrol. 2016;11:642-52. doi:10.2215/CJN.08530815.Rossignol P, Massy ZA, Azizi M, et al., ERA-EDTA EURECA-m Working Group, Red de Investigation Renal (REDINREN) Network, Cardiovascular and Renal Clinical Trialists (F-CRIN INI-CRCT) Network. The double challenge of resistant hypertension and chronic kidney disease. Lancet. 2015;386:1588-98. doi: 10.1016/S0140-6736(15)00418-3.Rossignol P, Massy ZA, Azizi M, et al., ERA-EDTA EURECA-m Working Group, Red de Investigation Renal (REDINREN) Network, Cardiovascular and Renal Clinical Trialists (F-CRIN INI-CRCT) Network. The double challenge of resistant hypertension and chronic kidney disease. Lancet. 2015;386:1588-98. doi: 10.1016/S0140-6736(15)00418-3.Schmieder RE, Mann JF, Schumacher H, et al., ONTARGET Investigators. Changes in albuminuria predict mortality and morbidity in patients with vascular disease. J Am Soc Nephrol. 2011;22:1353-64. doi:10.1681/ASN.2010091001.Schmieder RE, Mann JF, Schumacher H, et al., ONTARGET Investigators. Changes in albuminuria predict mortality and morbidity in patients with vascular disease. J Am Soc Nephrol. 2011;22:1353-64. doi:10.1681/ASN.2010091001.de Zeeuw D, Remuzzi G, Parving HH, et al. Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation 2004;110:921-7. doi:10.1161/01.CIR.0000139860.33974.28.de Zeeuw D, Remuzzi G, Parving HH, et al. Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation 2004;110:921-7. doi:10.1161/01.CIR.0000139860.33974.28.Bakris GL, Sarafidis PA, Weir MR, et al., ACCOMPLISH Trial Investigators. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial. Lancet. 2010;375:1173-81. doi:10.1016/S0140-6736(09)62100-0.Bakris GL, Sarafidis PA, Weir MR, et al., ACCOMPLISH Trial Investigators. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial. Lancet. 2010;375:1173-81. doi:10.1016/S0140-6736(09)62100-0.Hakam AC, Hussain T. Renal angiotensin II type-2 receptors are upregulated and mediate the candesartan-induced natriuresis/diuresis in obese Zucker rats. J Hypertens. 2005;45:270-5.Hakam AC, Hussain T. Renal angiotensin II type-2 receptors are upregulated and mediate the candesartan-induced natriuresis/diuresis in obese Zucker rats. J Hypertens. 2005;45:270-5.Сиренко Ю. Н., Донченко Н. В. Место кандесартана в современной терапии сердечно-сосудистых заболеваний: обзор доказательств. Артериальная гипертензия. 2011;4(18):114-26.Sirenko YuN, Donchenko NV. Candesartan's Place in Modern Cardiovascular Therapy: A Review of Evidence. Arterial hypertension. 2011;4(18):114-26. (In Russ)Burgess E, Muirhead N, de Cotret PR, et al. SMART (Supra Maximal Atacand Renal Trial) Investigators. Supramaximal dose of candesartan in proteinuric renal disease. J Am Soc Nephrol. 2009;20:893-900.Burgess E, Muirhead N, de Cotret PR, et al. SMART (Supra Maximal Atacand Renal Trial) Investigators. Supramaximal dose of candesartan in proteinuric renal disease. J Am Soc Nephrol. 2009;20:893-900.Mogensen CE, Neldam S, Tikkanen I, et al. For the CALM study group. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ. 2000;321:1440-4.Mogensen CE, Neldam S, Tikkanen I, et al. For the CALM study group. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ. 2000;321:1440-4.Song JH, Cha SH, Lee HJ, et al. Effect of low-dose dual blockade of renin-angiotensin system on urinary TGF-beta in type 2 diabetic patients with advanced kidney disease. Nephrology Dialysis Transplantation. 2006;21(3):683-9. doi:10.1093/ndt/gfi310.Song JH, Cha SH, Lee HJ, et al. Effect of low-dose dual blockade of renin-angiotensin system on urinary TGF-beta in type 2 diabetic patients with advanced kidney disease. Nephrology Dialysis Transplantation. 2006;21(3):683-9. doi:10.1093/ndt/gfi310.Philipp T, Martinez F, Geiger H, Moulin B, et al. Candesartan improves blood pressure control and reduces proteinuria in renal transplant recipients: results from SECRET. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association - European Renal Association. 2010;25:967-76. doi:10.1093/ndt/gfp581.Philipp T, Martinez F, Geiger H, Moulin B, et al. Candesartan improves blood pressure control and reduces proteinuria in renal transplant recipients: results from SECRET. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association - European Renal Association. 2010;25:967-76. doi:10.1093/ndt/gfp581.Beckett N, Peters R, Leonetti G, et al., HYVET Study Group. Subgroup and per-protocol analyses from the Hypertension in the Very Elderly Trial. J Hypertens. 2014;32:1478-87. doi:10.1097/HJH.0000000000000195.Beckett N, Peters R, Leonetti G, et al., HYVET Study Group. Subgroup and per-protocol analyses from the Hypertension in the Very Elderly Trial. J Hypertens. 2014;32:1478-87. doi:10.1097/HJH.0000000000000195.Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure-lowering treatment. 6. Prevention of heart failure and new-onset heart failure-meta-analyses of randomized trials. J Hypertens. 2016;34:373-84. doi:10.1097/HJH.0000000000000848.Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure-lowering treatment. 6. Prevention of heart failure and new-onset heart failure-meta-analyses of randomized trials. J Hypertens. 2016;34:373-84. doi:10.1097/HJH.0000000000000848.Bom belli M, Facchetti R, Cuspidi C, et al. Prognostic significance of left atrial enlargement in a general population: results of the PAMELA study. J Hypertens. 2014;64:1205-11. doi:10.1161/HYPERTENSIONAHA.114.03975.Bom belli M, Facchetti R, Cuspidi C, et al. Prognostic significance of left atrial enlargement in a general population: results of the PAMELA study. J Hypertens. 2014;64:1205-11. doi:10.1161/HYPERTENSIONAHA.114.03975.Soliman EZ, Byington RP, Bigger JT, et al. Effect of intensive blood pressure lowering on left ventricular hypertrophy in patients with diabetes mellitus: action to control cardiovascular risk in diabetes blood pressure trial. J Hypertens. 2015;66:1123-9. doi: 10.1161/HYPERTENSIONAHA.115.06236.Soliman EZ, Byington RP, Bigger JT, et al. Effect of intensive blood pressure lowering on left ventricular hypertrophy in patients with diabetes mellitus: action to control cardiovascular risk in diabetes blood pressure trial. J Hypertens. 2015;66:1123-9. doi: 10.1161/HYPERTENSIONAHA.115.06236.Verdecchia P, Staessen JA, Angeli F, et al. Cardio-Sis Investigators. Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial. Lancet. 2009;374:525-33.Verdecchia P, Staessen JA, Angeli F, et al. Cardio-Sis Investigators. Usual versus tight control of systolic blood pressure in non-diabetic patients with hypertension (Cardio-Sis): an open-label randomised trial. Lancet. 2009;374:525-33.Fagard RH, Celis H, Thijs L, Wouters S. Regression of left ventricular mass by antihypertensive treatment: a meta-analysis of randomized comparative studies. J Hypertension. 2009;54:1084-91. doi:10.1161/HYPERTENSIONAHA.109.136655.Fagard RH, Celis H, Thijs L, Wouters S. Regression of left ventricular mass by antihypertensive treatment: a meta-analysis of randomized comparative studies. J Hypertension. 2009;54:1084-91. doi:10.1161/HYPERTENSIONAHA.109.136655.Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129-200. doi:10.1093/eurheartj/ehw128.Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129-200. doi:10.1093/eurheartj/ehw128.Pfeifer MA, Swedberg K, Granger CB, et al. For the CHARM Investigators and Committees. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003;362:759-66. doi:10.1016/S0140-6736(03)14282-1.Pfeifer MA, Swedberg K, Granger CB, et al. For the CHARM Investigators and Committees. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003;362:759-66. doi:10.1016/S0140-6736(03)14282-1.McMurray JJV, Stergren J, Swedberg K, et al. For the CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced leftventricular systolic function taking angiotensinconvertingenzyme inhibitors: the CHARM-Added trial. Lancet. 2003;362:767-71. doi:10.1016/S0140-6736(03)14283-3.McMurray JJV, Stergren J, Swedberg K, et al. For the CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced leftventricular systolic function taking angiotensinconvertingenzyme inhibitors: the CHARM-Added trial. Lancet. 2003;362:767-71. doi:10.1016/S0140-6736(03)14283-3.Granger CB, McMurray JJV, Yusuf S, et al. For the CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced leftventricular systolic function intolerant to angiotensinconvertingenzyme inhibitors: the CHARM-Alternative trial. Lancet. 2003;362:772-6. doi:10.1016/S0140-6736(03)14284-5.Granger CB, McMurray JJV, Yusuf S, et al. For the CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced leftventricular systolic function intolerant to angiotensinconvertingenzyme inhibitors: the CHARM-Alternative trial. Lancet. 2003;362:772-6. doi:10.1016/S0140-6736(03)14284-5.Yusuf S, Pfeffer MA, Swedberg K, et al. for the CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and preserved leftventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362:777-81. doi:10.1016/S0140-6736(03)14285-7.Yusuf S, Pfeffer MA, Swedberg K, et al. for the CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and preserved leftventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003;362:777-81. doi:10.1016/S0140-6736(03)14285-7.Ducharme A, Swedberg K, Pfeffer MA, et al. CHARM Investigators. Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. Am Heart J. 2006;152:86-92. doi:10.1016/j.ahj.2005.06.036.Ducharme A, Swedberg K, Pfeffer MA, et al. CHARM Investigators. Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. Am Heart J. 2006;152:86-92. doi:10.1016/j.ahj.2005.06.036.

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