pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2016-26-1-85-91pulmo-677Research ArticleОБЗОРЫREVIEWРиоцигуат и силденафил в лечении легочной гипертензии: сходства и различияRiociguat and sildenafil for pulmonary hypertension: similarity and differenceШмальцА. А.Shmal'tsA. A.

д. м. н., ведущий научный сотрудник отделения хирургического лечения заболеваний сердца с прогрессирующей легочной гипертензией ФГБУ «Научный центр сердечно-сосудистой хирургии им. А.Н.Бакулева» Минздрава России, доцент кафедры сердечно-сосудистой хирургии ГБОУ ДПО «Российская медицинская академия последипломного образования» Минздрава России; тел.: (495) 414-79-33

MD, Chief Scientist at Department of Surgery of Heart Diseases with Progressive Pulmonary Hypertension, A.N.Bakulev Federal Academic Center of Cardiovascular Surgery, Healthcare Ministry of Russia; Associate Professor at Department of Cardiovascular Surgery, Russian State Medical Postgraduate Academy, Healthcare Ministry of Russia; tel.: (495) 414-79-33;

shmaltzanton@inbox.ruГорбачевскийС. В.GorbachevskiyS. V.

д. м. н., профессор, заведующий отделением хирургического лечения заболеваний сердца с прогрессирующей легочной гипертензией ФГБУ «Научный центр сердечно-сосудистой хирургии им. А.Н.Бакулева» Минздрава России, профессор кафедры сердечно-сосудистой хирургии ГБОУ ДПО «Российская медицинская академия последипломного образования» Минздрава России; тел.: (495) 414-78-19

MD, Professor, Head of Department of Surgery of Heart Diseases with Progressive Pulmonary Hypertension, A.N.Bakulev Federal Academic Center of Cardiovascular Surgery, Healthcare Ministry of Russia; Professor at Department of Cardiovascular Surgery, Russian State Medical Postgraduate Academy, Healthcare Ministry of Russia; tel.: (495) 414-78-19

svgorby@newmail.ruФГБУ «Научный центр сердечно-сосудистой хирургии имени А.Н.Бакулева» Минздрава России: 121552, Москва, Рублевское шоссе, 135; ГБОУ ДПО «Российская медицинская академия последипломного образования» Минздрава России: 125993, Москва, ул. Баррикадная, 2 / 1РоссияA.N.Bakulev Federal Academic Center of Cardiovascular Surgery, Healthcare Ministry of Russia: 135, Rublevskoe roadway, Moscow, 121552, Russia; Russian State Medical Postgraduate Academy, Healthcare Ministry of Russia: 2 / 1, Barrikadnaya str., Moscow, 123995, RussiRussian Federation2016190420162618591Copyright © Шмальц А.А., Горбачевский С.В., 20162016Шмальц А.А., Горбачевский С.В.Shmal'ts A.A., Gorbachevskiy S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/677

В клиническую практику последних десятилетий внедрены лекарственные препараты для лечения легочной гипертензии. При помощи силденафила происходит селективное ингибирование фосфодиэстеразы-5 (ФДЭ-5), увеличивается содержание циклического гуанозинмонофосфата (цГМФ) в стенке легочных сосудов, что приводит к вазодилатации, подавлению пролиферации и другим специфическим эффектам. Силденафил показан для моно- и последовательной комбинированной терапии легочной артериальной гипертензии (ЛАГ), что обусловлено его высокими классом рекомендаций и уровнем доказательности. Однако часть пациентов недостаточно отвечают на терапию ингибиторами ФДЭ-5. Высказано предположение, что хорошей альтернативой для таких больных могли бы стать стимуляторы растворимой гуанилатциклазы (рГЦ). Риоцигуат обладает двойным механизмом действия: во-первых, способствует повышению биосинтеза цГМФ посредством прямой стимуляции рГЦ, подобно оксиду азота (NO) и независимо от него; во-вторых, сенсибилизирует рГЦ к эндогенному NO путем стабилизации ее связи с NO. Риоцигуат показан для моно- и последовательной комбинированной терапии ЛАГ и терапии хронической тромбоэмболической легочной гипертензии, что также обусловлено его высокими классом рекомендаций и уровнем доказательности. В феврале 2014 г. стартовало клиническое исследование RESPITE, призванное оценить эффективность замены ингибиторов ФДЭ-5 на риоцигуат у пациентов с ЛАГ. К потенциально выгодным особенностям механизма действия риоцигуата относятся независимость от эндогенного NO при синтезе цГМФ и независимость от других (помимо ФДЭ-5) изоферментов фосфодиэстераз. Реализуются ли эти особенности механизма действия риоцигуата в клинические преимущества при лечении ЛАГ, покажет время и, возможно – исследование RESPITE.

Last decades, several drugs for treatment of pulmonary hypertension have been implemented in clinical practice. Sildenafil selectively inhibits phosphodiesterase-5 (PDE-5), increases cyclic guanosine monophosphate (cGMP) level in the pulmonary vascular wall leading to vasodilation, inhibition of proliferation and other specific effects. Sildenafil is indicated as single therapy and in sequential combination therapy of pulmonary arterial hypertension (PAH) (high-level evidence, high-class recommendation). However, therapeutic response on PDE-5 inhibitors is insufficient in a certain number of patients. Soluble guanylate cyclase (sGC) activators were proposed as a good alternative for such patients. Riociguat has dual mechanism of action: firstly, it is designed to increase cGMP biosynthesis via direct activation of sGC; this pathway resembles that of nitric oxide (NO) but is independent on NO. Secondly, riociguat can sensitise sGC to NO. Riociguat is indicated as single therapy and in sequential combination therapy of PAH and to treatment of chronic thromboembolic pulmonary hypertension (high-level evidence, high-class recommendation). A clinical trial RESPITE has been initiated in February, 2014, which is intended to evaluate efficacy of switching PAH patients from PDE-5 inhibitors to riociguat. Potential advantage of this drug is the mechanism independent of NO and of other PDE enzyme isoforms. Whether this advantage is clinically significant, remains to be seen, probably, in the RESPITE trial.

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