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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">rpcardio</journal-id><journal-title-group><journal-title xml:lang="en">Rational Pharmacotherapy in Cardiology</journal-title><trans-title-group xml:lang="ru"><trans-title>Рациональная Фармакотерапия в Кардиологии</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1819-6446</issn><issn pub-type="epub">2225-3653</issn><publisher><publisher-name>«SILICEA-POLIGRAF» LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.20996/1819-6446-2021-04-03</article-id><article-id custom-type="elpub" pub-id-type="custom">rpcardio-2428</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL STUDIES</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group></article-categories><title-group><article-title>Treatment of Resistant Hypertension in Real Clinical Settings</article-title><trans-title-group xml:lang="ru"><trans-title>Фармакотерапия резистентной артериальной гипертензии в реальной клинической практике</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1215-132X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мальцева</surname><given-names>А. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Maltseva</surname><given-names>A. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мальцева Александра Сергеевна</p><p>Москва</p></bio><bio xml:lang="en"><p>Alexandra S. Maltseva</p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3766-1868</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Цыганкова</surname><given-names>А. Э.</given-names></name><name name-style="western" xml:lang="en"><surname>Tsygankova</surname><given-names>A. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Цыганкова Анна Эдуардовна - eLibrary SPIN 6583-0476</p><p>Москва</p></bio><bio xml:lang="en"><p>Anna E. Tsygankova - eLibrary SPIN 6583-0476</p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3299-4743</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Габитова</surname><given-names>М. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Gabitova</surname><given-names>M. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Габитова Мария Александровна – eLibrary SPIN 4536-4690</p><p>Москва</p></bio><bio xml:lang="en"><p>Mariia A. Gabitova - eLibrary SPIN 4536-4690</p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1565-5440</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Родионов</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Rodionov</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Родионов Антон Владимирович – eLibrary SPIN 5063-0847</p><p>Москва</p></bio><bio xml:lang="en"><p>Anton V. Rodionov - eLibrary SPIN 5063-0847</p><p>Moscow</p></bio><email xlink:type="simple">avrodion@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2682-4417</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Фомин</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Fomin</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Фомин Виктор Викторович – eLibrary 8465-2747</p><p>Москва</p></bio><bio xml:lang="en"><p>Victor V. Fomin - eLibrary 8465-2747</p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>I.M. Sechenov First Moscow State Medical University (Sechenov University)</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>05</day><month>05</month><year>2021</year></pub-date><volume>17</volume><issue>2</issue><fpage>200</fpage><lpage>205</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Maltseva A.S., Tsygankova A.E., Gabitova M.A., Rodionov A.V., Fomin V.V., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Мальцева А.С., Цыганкова А.Э., Габитова М.А., Родионов А.В., Фомин В.В.</copyright-holder><copyright-holder xml:lang="en">Maltseva A.S., Tsygankova A.E., Gabitova M.A., Rodionov A.V., Fomin V.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.rpcardio.online/jour/article/view/2428">https://www.rpcardio.online/jour/article/view/2428</self-uri><abstract><sec><title>Background</title><p>Background. Current guidelines describe in detail the approaches to the management of patients with resistant hypertension, however, in real clinical settings the number of non-rational and ineffective combinations of antihypertensive drugs used remains high.</p></sec><sec><title>Aim</title><p>Aim. To analyze the distribution of different combinations of antihypertensive drugs for the treatment of resistant hypertension and to estimate the proportion of non-rational combinations.</p></sec><sec><title>Methods</title><p>Methods. The retrospective analysis includes 117 outpatients with resistant hypertension. Resistant hypertension was defined as blood pressure that remains above goal despite concurrent use of three antihypertensive agents of different classes. Exclusion criteria was secondary hypertension. We defined rational combination as the standard combination (renin-angiotensin system [RAS] blocker + calcium-channel blocker [CCB] + diuretic) plus one of the group of reserve drugs (mineralocorticoid receptors antagonist [MRA], beta-blocker, alpha-blocker, agonist of imidazoline receptors [AIR]). Non-rational were considered combinations in which reserve drugs were used before the appointment of a triple combination of first-line drugs. Moreover, in a subgroup of non-rational therapy, situations were identified where such a combination was justified.</p></sec><sec><title>Results</title><p>Results. The proportion of rational combinations was 58.9%, reasonably non-rational - 15.5%, unreasonably non-rational - 25.6%. Unreasonably non-rational combinations are distributed as follows: non-appointment of CCB - 12%, non-appointment of RAS-blockers - 8%, non-appointment of diuretics - 6%, use of RAS-blockers for hyperkalemia - 6%, administration of MRA without non-potassium-sparing diuretics - 5%, double blockade of RAS - 3%, other combinations - 7%. In addition to first-line drugs, beta-blockers (93.2%), loop diuretics (22.2%), AIR (21.4) were the most prescribable, while the proportion of MRA is only 15.4% of the entire sample.</p></sec><sec><title>Limitation</title><p>Limitation: some patient's characteristics could be missed in case histories and some of the combinations could be falsely recognized as malpractice since the analysis was conducted retrospectively.</p></sec><sec><title>Conclusion</title><p>Conclusion. The proportion of the non-rational combinations for the treatment of resistant hypertension is high. Among the drugs of the reserve, the frequent use of beta-blockers and moxonidine and the inadequate administration of spironolactone are noteworthy. The problem of treatment strategy choice remains relevant in real clinical practice.</p></sec></abstract><trans-abstract xml:lang="ru"><p>Современные клинические рекомендации достаточно подробно описывают подходы к ведению пациентов с резистентной артериальной гипертензией (РАГ), тем не менее, в реальной клинической практике количество используемых нерациональных и неэффективных комбинаций антигипертензивных препаратов (АГП) остается высоким.</p><sec><title>Цель</title><p>Цель. Изучить частоту назначения различных комбинаций АГП у больных РАГ, определить долю назначения нерациональных комбинаций и их особенности.</p></sec><sec><title>Материал и методы</title><p>Материал и методы. Проведен ретроспективный анализ медицинской документации 117 амбулаторных пациентов с РАГ, которую определяли как недостижение целевого артериального давления (АД) на фоне приема трех и более АГП. Критерием исключения был установленный диагноз вторичной артериальной гипертензии.</p><p>В качестве рациональной комбинации АГП рассматривали сочетание препаратов первого ряда (блокатор ренин-ангиотензиновой системы [РАС]+антагонист кальция [АК]+диуретик) с одной из групп препаратов резерва (антагонист минералокортикоидных рецепторов [АМР], бета-блокатор, альфа-блокатор, агонист имидазолиновых рецепторов [АИР]). Нерациональными считали комбинации, в которых препараты резерва использовали до назначения тройной комбинации препаратов первого ряда. При этом в подгруппе нерациональной терапии выделяли ситуации, когда такое сочетание было обосновано.</p></sec><sec><title>Результаты</title><p>Результаты. Доля пациентов, получавших рациональную комбинацию АГП составила 58,9%, обоснованно нерациональную - 15,5%, необоснованно нерациональную - 25,6%. Необоснованно нерациональные комбинации распределены следующем образом: не назначение АК - 12%, не назначение блокатора РАС - 8%, не назначение диуретиков - 6%, применение блокаторов РАС при гиперкалиемии - 6%, назначение АМР без не-калийсберегающих диуретиков - 5%, двойная блокада РАС - 3%, другие комбинации - 7%. В назначениях, помимо препаратов первого ряда, превалируют бета-адреноблокаторы (93,2%), петлевые диуретики (22,2%), АИР (21,4), тогда как доля АМР составляет лишь 15,4% от всей выборки.</p></sec><sec><title>Заключение</title><p>Заключение. В назначениях у пациентов с РАГ отмечается большая доля нерациональных комбинаций АГП. Среди препаратов резерва обращает внимание частое назначение бета-адреноблокаторов и моксонидина и недостаточное назначение спиронолактона. Необходима актуализация темы лечения РАГ для врачей первичного звена.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>резистентная артериальная гипертензия</kwd><kwd>артериальная гипертензия</kwd><kwd>фармакотерапия</kwd><kwd>лечение.</kwd></kwd-group><kwd-group xml:lang="en"><kwd>resistant arterial hypertension</kwd><kwd>hypertension</kwd><kwd>pharmacotherapy</kwd><kwd>treatment</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Муромцева Г.А., Концевая А.В., Константинов В.В., и др. Распространенность факторов риска неинфекционных заболеваний в российской популяции в 2012-2013гг. Результаты исследования ЭССЕ-РФ. Кардиоваскулярная Терапия и Профилактика. 2014;13(6):4-11. DOI:10.15829/1728-8800-2014-6-4-11.</mixed-citation><mixed-citation xml:lang="en">Muromtseva GA, Kontsevaya AV, Konstantinov VV, et al. The prevalence of non-infectious diseases risk factors in Russian population in 2012-2013 years. The results of ECVD-RF. Cardiovascular Therapy and Prevention. 2014;13(6):4-11 (In Russ.) DOI:10.15829/1728-8800-2014-6-4-11.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Williams B, Mancia G, Spiering W, et al. ESC Scientific Document Group.2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J. 2018;39(33):3021-104. DOI:10.1093/eurheartj/ehy339.</mixed-citation><mixed-citation xml:lang="en">Williams B, Mancia G, Spiering W, et al. ESC Scientific Document Group.2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J. 2018;39(33):3021-104. DOI:10.1093/eurheartj/ehy339.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Bohm M, Kario K, Kandzari DE, et al. SPYRAL HTN-OFF MED Pivotal Investigators. Efficacy of catheterbased renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet. 2020;395(10234):1444-51. DOI:10.1016/S0140-6736(20)30554-7.</mixed-citation><mixed-citation xml:lang="en">Bohm M, Kario K, Kandzari DE, et al. SPYRAL HTN-OFF MED Pivotal Investigators. Efficacy of catheterbased renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet. 2020;395(10234):1444-51. DOI:10.1016/S0140-6736(20)30554-7.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Bobrie G, Frank M, Azizi M, et al. Sequential nephron blockade versus sequential renin-angiotensin system blockade in resistant hypertension: a prospective, randomized, open blinded endpoint study. J Hypertens. 2012;30(8):1656-64. DOI:10.1097/HJH.0b013e3283551e98.</mixed-citation><mixed-citation xml:lang="en">Bobrie G, Frank M, Azizi M, et al. Sequential nephron blockade versus sequential renin-angiotensin system blockade in resistant hypertension: a prospective, randomized, open blinded endpoint study. J Hypertens. 2012;30(8):1656-64. DOI:10.1097/HJH.0b013e3283551e98.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Vac^k J, Sedlak R, Jarkovsky J, et al. Effect of spironolactone in resistant arterial hypertension: a ran-domized, double-blind, placebo-controlled trial (ASPIRANT-EXT). Medicine (Baltimore). 2014;93(27):e162. DOI:10.1097/MD.0000000000000162.</mixed-citation><mixed-citation xml:lang="en">Vac^k J, Sedlak R, Jarkovsky J, et al. Effect of spironolactone in resistant arterial hypertension: a ran-domized, double-blind, placebo-controlled trial (ASPIRANT-EXT). Medicine (Baltimore). 2014;93(27):e162. DOI:10.1097/MD.0000000000000162.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Williams B, MacDonald TM, Morant S, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;386(10008):2059-68. DOI:10.1016/S0140-6736(15)00257-3.</mixed-citation><mixed-citation xml:lang="en">Williams B, MacDonald TM, Morant S, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;386(10008):2059-68. DOI:10.1016/S0140-6736(15)00257-3.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Krieger EM, Drager LF, Giorgi DMA, et al. ReHOT Investigators. Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment). Hypertension. 2018;71(4):681-90. DOI:10.1161/HYPERTENSION-AHA.117.10662.</mixed-citation><mixed-citation xml:lang="en">Krieger EM, Drager LF, Giorgi DMA, et al. ReHOT Investigators. Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment). Hypertension. 2018;71(4):681-90. DOI:10.1161/HYPERTENSION-AHA.117.10662.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Carey RM, Calhoun DA, Bakris GL, et al. Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association. Hypertension. 2018;72(5):e53- e90. DOI:10.1161/HYP.0000000000000084.</mixed-citation><mixed-citation xml:lang="en">Carey RM, Calhoun DA, Bakris GL, et al. Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association. Hypertension. 2018;72(5):e53- e90. DOI:10.1161/HYP.0000000000000084.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Manolis AA, Manolis TA, Melita H, Manolis AS. Eplerenone Versus Spironolactone in Resistant Hypertension: an Efficacy and/or Cost or Just a Men's Issue? Curr Hypertens Rep. 2019;21(3):22. DOI:10.1007/s11906-019-0924-0.</mixed-citation><mixed-citation xml:lang="en">Manolis AA, Manolis TA, Melita H, Manolis AS. Eplerenone Versus Spironolactone in Resistant Hypertension: an Efficacy and/or Cost or Just a Men's Issue? Curr Hypertens Rep. 2019;21(3):22. DOI:10.1007/s11906-019-0924-0.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Dahlof B, Sever PS, Poulter NR, et al.; ASCOT Investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicenter randomized controlled trial. Lancet. 2005;366:895- 906. DOI:10.1016/S0140-6736(05)67185-1.</mixed-citation><mixed-citation xml:lang="en">Dahlof B, Sever PS, Poulter NR, et al.; ASCOT Investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicenter randomized controlled trial. Lancet. 2005;366:895- 906. DOI:10.1016/S0140-6736(05)67185-1.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Sundstrom J, Arima H, Woodward M, et al. for the Blood Pressure Lowering Treatment Trialists' Collaboration. Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet. 2014;384:591-8. DOI:10.1016/S0140-6736(14)61212-5.</mixed-citation><mixed-citation xml:lang="en">Sundstrom J, Arima H, Woodward M, et al. for the Blood Pressure Lowering Treatment Trialists' Collaboration. Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet. 2014;384:591-8. DOI:10.1016/S0140-6736(14)61212-5.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">ALLHAT Officers and Coordinators for the 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. DOI:10.1001/jama.288.23.2981.</mixed-citation><mixed-citation xml:lang="en">ALLHAT Officers and Coordinators for the 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. DOI:10.1001/jama.288.23.2981.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Cohn JN, Pfeffer MA, Rouleau J, et al.; MOXCON Investigators. Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail. 2003;5(5):659-67. DOI:10.1016/S1388-9842(03)00163-6.</mixed-citation><mixed-citation xml:lang="en">Cohn JN, Pfeffer MA, Rouleau J, et al.; MOXCON Investigators. Adverse mortality effect of central sympathetic inhibition with sustained-release moxonidine in patients with heart failure (MOXCON). Eur J Heart Fail. 2003;5(5):659-67. DOI:10.1016/S1388-9842(03)00163-6.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Martin U, Hill C, O'Mahony D. Use of moxonidine in elderly patients with resistant hypertension. J Clin Pharm Ther. 2005;30(5):433-7. DOI:10.1111/j.1365-2710.2005.00672.x.</mixed-citation><mixed-citation xml:lang="en">Martin U, Hill C, O'Mahony D. Use of moxonidine in elderly patients with resistant hypertension. J Clin Pharm Ther. 2005;30(5):433-7. DOI:10.1111/j.1365-2710.2005.00672.x.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">ONTARGET Investigators, Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358:1547-59. DOI:10.1056/NEJMoa0801317.</mixed-citation><mixed-citation xml:lang="en">ONTARGET Investigators, Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358:1547-59. DOI:10.1056/NEJMoa0801317.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Fried LF, Emanuele N, Zhang JH, et al.; VA NEPHRON-D Investigators. Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy. N Engl J Med. 2013;369:1892-1903. DOI:10.1056/NEJMoa1303154.</mixed-citation><mixed-citation xml:lang="en">Fried LF, Emanuele N, Zhang JH, et al.; VA NEPHRON-D Investigators. Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy. N Engl J Med. 2013;369:1892-1903. DOI:10.1056/NEJMoa1303154.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
