Optimization of specific therapy for pulmonary hypertension: the possibilities of riociguat

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Abstract

Pulmonary hypertension (PH) is a severe and often rapidly progressive disease with fatal outcome. Endothelial dysfunction in PH is associated with decreased nitric oxide production. After reviewing the mechanisms of action and the evidence base for specific therapy with phosphodiesterase 5 inhibitors (PDE-5) and soluble guanylate cyclase stimulators, a reseach review on switching from PDE-5 to riociguat is conducted. A potential advantage of riociguat is its independence from endogenous nitric oxide and from the other (besides PDE-5) isoenzymes of phosphodiesterases. The favorable efficacy profile of sildenafil has been proven for the main forms of pulmonary arterial hypertension, of riociguat – for the main forms of pulmonary arterial hypertension and chronic thromboembolic PH. The clinical efficacy of replacing PDE-5 with riociguat has been demonstrated in uncontrolled trials and in the randomized controlled study REPLACE. The possibility of therapy optimization by switching from IFDE-5 to riociguat is fixed in the Russian (class and level of evidence B-3) and Eurasian (class and level of evidence IIb-B) clinical guidelines, as well as in the materials of the Cologne Expert Consensus. An additional argument for switching is the lower cost as compared to combination therapy in the Russian Federation. According to the Russian and Eurasian guidelines for PH and the Russian instructions for the use of riociguat, the drug should be taken at least 24 hours after sildenafil discontinuation.

About the authors

Tamila V. Martynyuk

National Medical Research Center of Cardiology; Pirogov Russian National Research Medical University

Author for correspondence.
Email: trukhiniv@mail.ru
ORCID iD: 0000-0002-9022-8097

д-р мед. наук, рук. отд. легочной гипертензии и заболеваний сердца Института клинической кардиологии им. А.Л. Мясникова ФГБУ «НМИЦ кардиологии»; проф. каф. кардиологии ФДПО ФГАОУ ВО «РНИМУ им. Н.И. Пирогова»

Russian Federation, Moscow; Moscow

Anton A. Shmalts

Bakoulev National Medical Research Center of Cardiovascular Surgery; Russian Medical Academy of Continuous Professional Education

Email: trukhiniv@mail.ru
ORCID iD: 0000-0001-8937-1796

д-р мед. наук, вед. науч. сотр. отд-ния хирургического лечения заболеваний сердца с прогрессирующей легочной гипертензией ФГБУ «НМИЦ ССХ им. А.Н. Бакулева»; доц. каф. сердечно-сосудистой хирургии ФГБОУ ДПО РМАНПО

Russian Federation, Moscow; Moscow

Sergey V. Gorbachevsky

Bakoulev National Medical Research Center of Cardiovascular Surgery; Russian Medical Academy of Continuous Professional Education

Email: trukhiniv@mail.ru
ORCID iD: 0000-0002-4193-3320

д-р мед. наук, проф., зав. отд-нием хирургического лечения заболеваний сердца с прогрессирующей легочной гипертензией ФГБУ «НМИЦ ССХ им. А.Н. Бакулева»; проф. каф. сердечно-сосудистой хирургии ФГБОУ ДПО РМАНПО

Russian Federation, Moscow; Moscow

Irina E. Chazova

National Medical Research Center of Cardiology

Email: trukhiniv@mail.ru
ORCID iD: 0000-0002-9822-4357

акад. РАН, д-р мед. наук, проф., зам. ген. дир. по научно-экспертной работе, рук. отд. гипертонии Института клинической кардиологии им. А.Л. Мясникова ФГБУ «НМИЦ кардиологии»

Russian Federation, Moscow

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2. Fig. 1. Biochemical pathway of nitric oxide (NO) in health and in pulmonary hypertension (PH). Advantages of NO-independent action of soluble guanylate cyclase (sGC) stimulants over phosphodiesterase type 5 inhibitors (iPDE-5) (modified according to J. Stasch et al. [7], J. Schlossmann, E. Schuner [8] and O. Evgenov et al. [9]).

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3. Fig. 2. The negative effect of oxidative stress on vasodilation (modified according to J. Stasch et al. [7]). In PH, impaired vasodilation can also be seen even with a sufficient amount of endogenous NO.

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4. Fig. 3. Proportion of patients who achieved the combined primary endpoint in the REPLACE RCT [57].

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