pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2018-28-1-96-103pulmo-966Research ArticleОБЗОРЫREVIEWЭпоха двойной бронходилатации: первые прямые сравнения и метаанализыThe epoch of dual bronchodilation: the first direct comparisons and meta-analyzesВизельА. А.Vizel'A. A.

Визель Александр Андреевич – доктор медицинских наук, профессор, заведующий кафедрой фтизиопульмонологии. 

420012, Казань, ул. Бутлерова, 49.

Aleksandr A. Vizel', Doctor of Medicine, Professor, Head of Department of Phthisiology and Pulmonology/

ul. Butlerova 49, Kazan', 420012, Tatarstan Republic.

lordara@inbox.ruВизельИ. Ю.Vizel'I. Yu.

Визель Ирина Юрьевна – доктор медицинских наук, ассистент кафедры фтизиопульмонологии.

420012, Казань, ул. Бутлерова, 49.

Irina Yu. Vizel', Doctor of Medicine, Assistant Lecturer, Department of Phthisiology and Pulmonology.

ul. Butlerova 49, Kazan', 420012, Tatarstan Republic.

tatpulmo@mail.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Казанский государственный медицинский университет» Министерства здравоохранения Российской Федерации.РоссияKazan’ State Medical University, Healthcare Ministry of Russia.Russian Federation20182704201828196103Copyright © Визель А.А., Визель И.Ю., 20182018Визель А.А., Визель И.Ю.Vizel' A.A., Vizel' I.Y.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/966

Целью данного обзора литературных источников явилось обобщение публикаций последних лет по применению двойной бронходилатации у пациентов с хронической обструктивной болезнью легких. Регуляторными органами России, Европы и США одобрены 4 фиксированные комбинации длительно действующих β2-агонистов (ДДБА) и длительно действующих антихолинергических препаратов (ДДАХП) – вилантерол / умеклидиний, олодатерол / тиотропий, гликопирроний / индакатерол и формотерол / аклидиний. Непрямые сопоставления влияния этих комбинаций на параметры форсированного выдоха свидетельствуют о сопоставимом бронхолитическом эффекте. Отмечены различия свойств ингаляторов, применявшихся для каждой из комбинаций; при этом ингалятор Респимат отличался высокой и эффективной легочной депозицией, а дозирующий порошковый ингалятор (ДПИ) Эллипта – простотой в обучении и использовании и низкой частотой критических ошибок. В доступной литературе выявлены 3 прямых сравнения ДДБА / ДДАХП. По результатам прямого открытого сравнительного исследования неменьшей эффективности вилантерола / умеклидиния по сравнению с олодатеролом / тиотропием установлены преимущества вилантерола умеклидиния в ДПИ Эллипта. В 2 идентичных прямых сравнительных исследованиях гликопиррония / индакатерола 27,5 / 15,6 мкг 2 раза в день и вилантерола / умеклидиния 25 / 62,5 мкг 1 раз в день первичной конечной точки неменьшей эффективности не достигнуто, оценка вторичных конечных точек носила описательный характер. Различия между группами были небольшими и признаны клинически незначимыми. По результатам метаанализов и прямых сравнительных исследований пока нет возможности назвать лидирующий препарат двойной бронходилатации, поскольку его эффективность определяется многими факторами. Первым шагом в этом направлении стало прямое открытое сравнительное исследование, по результатам которого показано превосходство вилантерола / умеклидиния в ингаляторе Эллипта над олодотеролом / тиотропием в ингаляторе Респимат.

The aim of this review was to summarize recently published data on dual bronchodilation in patients with chronic obstructive pulmonary disease (COPD). Four fixed combinations of long-acting β2-agonists (LABA) and long-acting muscarinic receptor agonists (LAMA), vilanterol/umeclidinium, olodaterol/tiotropium, glycopyrronium/indacaterol, and formoterol/aclidinium, have been approved by regulatory organs of Russia, Europe, and USA. Indirect comparisons of effects of these combinations on forced expiratory parameters showed equal bronchodilation. Inhalational devices for each combination are different. Respimat soft-mist inhaler was characterized by high and effective drug deposition in the lungs, Ellipta dry powder inhaler was easy-to-use and was characterized by a low rate of crucial mistakes with the inhaler technique. We found three published direct comparative studies of LABA/LAMAs. An open-label direct non-inferiority study of vilanterol/umeclidinium vs olodaterol/tiotropium showed advantages of vilanterol/umeclidinium Ellipta inhaler. Two similar direct comparative trials of glycopyrronium/indacaterol 27.5/15.6 µg b.i.d. vs vilanterol/umeclidinium 25/62.5 µg q.d. did not reach the primary endpoint of non-inferiority; secondary endpoints were descriptive. Between-group differences were small and statistically insignificant. Conclusion. The results of meta-analyses and direct comparative trials are not sufficient to choose the best dual bronchodilator as the drug efficacy is determined by multiple factors. A direct open-label comparative trial that demonstrated superiority of vilanterol/umeclidinium Ellipta inhaler over olodaterol/tiotropium Respimat inhaler became the first step on this way.

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