Overview of Riociguat and Its Role in the Treatment of Pulmonary Hypertension

Pulmonary hypertension (PH), which includes pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), is a progressive condition with significant morbidity and mortality due to right heart failure if left untreated. Riociguat is a soluble guanylate cyclase (sGC) stimulator and is the only treatment approved for both PAH and CTEPH. The objectives of this review are to describe the epidemiology and pathophysiology of PAH and CTEPH; synthesize the pharmacology, efficacy, safety, and utilization of riociguat; and discuss the role of the pharmacist in managing patients with these conditions. Data presented in this review is supported by peer reviewed literature, using PubMed and key words including pulmonary hypertension, pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and riociguat. The review draws on key studies and review articles that discuss the pathophysiology of PAH and CTEPH, as well as articles discussing the safety and efficacy of riociguat. The overall goal in the treatment of PAH and CTEPH is to improve long-term survival. Treatment planning depends on the type of PH, treatment goals, comorbidities, and risk profiles. Pharmacists serve a valuable role as part of the multidisciplinary team in the care of patients with PH, many of whom may have comorbidities that contribute to high costs and resource utilization. Riociguat is a first-in-class medication and the only approved treatment for both PAH and CTEPH. In clinical trials, riociguat has demonstrated favorable efficacy and tolerability. Riociguat is a valuable addition to the armamentarium of options for treating patients with PH.

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Long-term survival in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Insights from a referral center in Portugal

Revista Portuguesa de Cardiologia ◽

10.1016/j.repc.2018.02.009 ◽

2018 ◽

Vol 37 (9) ◽

pp. 749-757 ◽

Cited By ~ 6

Author(s):

Mário Santos ◽

Ana Gomes ◽

Célia Cruz ◽

Joana Rocha ◽

Miguel Ricardo ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Term Survival ◽

Long Term Survival ◽

Referral Center ◽

Thromboembolic Pulmonary Hypertension ◽

Pulmonary Arterial

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Long-term survival in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Insights from a referral center in Portugal

Revista Portuguesa de Cardiologia (English Edition) ◽

10.1016/j.repce.2018.02.019 ◽

2018 ◽

Vol 37 (9) ◽

pp. 749-757

Author(s):

Mário Santos ◽

Ana Gomes ◽

Célia Cruz ◽

Joana Rocha ◽

Miguel Ricardo ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Term Survival ◽

Long Term Survival ◽

Referral Center ◽

Thromboembolic Pulmonary Hypertension ◽

Pulmonary Arterial

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Chronic thromboembolic pulmonary hypertension: a distinct disease entity

European Respiratory Review ◽

10.1183/16000617.00001115 ◽

2015 ◽

Vol 24 (136) ◽

pp. 246-252 ◽

Cited By ~ 53

Author(s):

Irene Lang

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Right Heart Failure ◽

Pulmonary Vasculature ◽

Distinct Disease ◽

Thromboembolic Pulmonary Hypertension ◽

Perfusion Scan ◽

Pulmonary Arterial

Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct subtype of pulmonary hypertension (PH). One disease hypothesis is that CTEPH results from the non-resolution of venous thromboembolism. CTEPH is characterised by the presence of obstructive fibrotic thromboembolic material in the major pulmonary vessels, with concomitant microvascular arteriopathy, resulting in progressive PH. The clinical presentation of CTEPH is similar to pulmonary arterial hypertension with nonspecific symptoms, but it is distinguished from pulmonary arterial hypertension by the presence of mismatched segmental defects on the ventilation/perfusion scan. The exact prevalence and incidence of CTEPH are unknown, but are thought to have been underestimated in the past. CTEPH is unique among the subgroups of PH in that it is potentially curable with pulmonary endarterectomy, a surgical intervention intended to remove the occlusive material from the pulmonary vasculature. However, in some patients the obstructions are technically inaccessible or the risk/benefit ratios are unfavourable, making the condition inoperable. It is thought that the involvement of the smaller, more distal vessels is a target for medical treatment. Untreated, CTEPH may result in right heart failure and death. The pathophysiological mechanisms which cause CTEPH are complex and have not yet been fully elucidated.

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Medical Management of Pulmonary Arterial Hypertension

10.2310/im.1646 ◽

2018 ◽

Author(s):

Inderjit Singh ◽

Aaron B Waxman

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Medical Management ◽

Soluble Guanylate Cyclase ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Endothelin Receptor ◽

Prostacyclin Receptor ◽

Thromboembolic Pulmonary Hypertension ◽

Pulmonary Arterial

The medical management of pulmonary arterial hypertension (PAH) has advanced considerably over the years. Once the diagnosis of PAH is made, the medical management includes both conventional and PAH-pathway specific therapies. Five different classes of drugs are now available targeting the endothelin, prostacyclin, and nitric oxide pathways (i.e. endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, prostacyclin analogues, and prostacyclin receptor agonists). These targeted therapies are approved for treatment of patients with PAH and chronic thromboembolic pulmonary hypertension (CTEPH) only. Long-term and event-driven studies of novel drugs have led to further improvement in the medical management of PAH and CTEPH. In this review, we will focus on the medical management of patients with PAH and CTEPH. This review contains 4 figures, 6 Tables and 30 references Keywords: Pulmonary arterial hypertension, Chronic thromboembolic pulmonary hypertension, Medical management, Pulmonary vasodilators, Phosphodiesterase inhibitor, Soluble guanylate cyclase stimulator, Endothelin receptor antagonist, Prostacyclin receptor agonist

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Riociguat For Chronic Thromboembolic Pulmonary Hypertension And Pulmonary Arterial Hypertension: First Long-term Extension Data From A Phase II Study

10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a6770 ◽

2010 ◽

Author(s):

Hossein-Ardeschir Ghofrani ◽

Marius M. Hoeper ◽

Michael Halank ◽

F J. Meyer ◽

Gerd Staehler ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Phase Ii ◽

Phase Ii Study ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Thromboembolic Pulmonary Hypertension ◽

Pulmonary Arterial

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Riociguat For Chronic Thromboembolic Pulmonary Hypertension And Pulmonary Arterial Hypertension: Long-Term Safety, Tolerability, And Efficacy

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a2370 ◽

2012 ◽

Cited By ~ 1

Author(s):

Hossein A. Ghofrani ◽

Marius M. Hoeper ◽

Michael Halank ◽

F. Joachim Meyer ◽

Gerd Stahler ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Thromboembolic Pulmonary Hypertension ◽

Pulmonary Arterial

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Riociguat for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Results from a phase II long-term extension study

Respiratory Medicine ◽

10.1016/j.rmed.2017.05.008 ◽

2017 ◽

Vol 128 ◽

pp. 50-56 ◽

Cited By ~ 18

Author(s):

Michael Halank ◽

Marius M. Hoeper ◽

Hossein-Ardeschir Ghofrani ◽

F. Joachim Meyer ◽

Gerd Stähler ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Phase Ii ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Extension Study ◽

Thromboembolic Pulmonary Hypertension ◽

Pulmonary Arterial

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Long-term Riociguat administration reduces right heart size in Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: a retrospective single-center analysis.

Pneumologie ◽

10.1055/s-0035-1544900 ◽

2015 ◽

Vol 69 (S 01) ◽

Author(s):

B Egenlauf ◽

A Marra ◽

N Ehlken ◽

C Fischer ◽

C Nagel ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Single Center ◽

Right Heart ◽

Thromboembolic Pulmonary Hypertension ◽

Heart Size ◽

Pulmonary Arterial

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The achievements of the modern specific therapy of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: focus on the stimulator of soluble guanylate cyclase riociguat

Terapevticheskii arkhiv ◽

10.26442/00403660.2020.09.000717 ◽

2020 ◽

Vol 92 (9) ◽

pp. 77-84

Author(s):

S. E. Gratsianskaya ◽

Z. S. Valieva ◽

T. V. Martynyuk

Keyword(s):

Clinical Trials ◽

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Guanylate Cyclase ◽

Soluble Guanylate Cyclase ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

No Production ◽

Thromboembolic Pulmonary Hypertension ◽

Pulmonary Arterial

Currently, treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) is focused on three signaling pathways: the NO pathway, the endothelin pathway, and the prostacyclin pathway. Riociguat is the only representative of stimulators of the soluble guanylate cyclase (sGC) class that is approved for the treatment of PAH and inoperable and persistent/recurrent CTEPH. The review presents data from clinical trials showing a positive effect of riociguat on the functional and hemodynamic profile of patients with PAH and CTEPH. In recent years there has been much discussion about the possibility of optimizing therapy by switching to drugs that affect a single pathogenesis target. Thus, sGC stimulants have obvious advantages over phosphodiesterase type 5 (PDE-5) inhibitors, including the ability of riociguat to exert pharmacological effects (due to a NO-independent mechanism of action) even in conditions of reduced NO production. Switching from PDE-5 to riociguat may be safe and appropriate, according to clinical trials presented in the review. In accordance with the guidelines for the diagnosis and treatment of pulmonary hypertension of the Eurasian Association of cardiologists from 2019, this strategy is approved when PDE5 therapy is ineffective in patients with PAH FC III (WHO).

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