scholarly journals Modulation of soluble guanylate cyclase ameliorates pulmonary hypertension in a rat model of chronic thromboembolic pulmonary hypertension by stimulating angiogenesis

2022 ◽  
Vol 10 (1) ◽  
Author(s):  
John Zagorski ◽  
Evandro Neto‐Neves ◽  
Nathan J. Alves ◽  
Amanda J. Fisher ◽  
Jeffrey A. Kline
Keyword(s):  
Pulmonary Hypertension ◽  
Guanylate Cyclase ◽  
Rat Model ◽  
Soluble Guanylate Cyclase ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Thromboembolic Pulmonary Hypertension

scholarly journals The soluble guanylate cyclase stimulator riociguat is the first-line therapy for chronic thromboembolic pulmonary hypertension patients

Kardiologiia ◽  
2020 ◽  
Vol 60 (8) ◽  
pp. 115-123
Author(s):  
Z. S. Valieva ◽  
S. E. Gratsianskaya ◽  
T. V. Martynyuk
Keyword(s):  
Pulmonary Hypertension ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Pulmonary Arteries ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
First Line ◽  
Pulmonary Thromboendarterectomy ◽  
First Line Therapy ◽  
Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Microcirculation

Chronic thromboembolic pulmonary hypertension (CTEPH) is a precapillary type of pulmonary hypertension with chronic obstruction of large and medium branches of pulmonary arteries along with secondary alterations in pulmonary microcirculation, which cause progressive increases in pulmonary vascular resistance and pulmonary arterial pressure and ensuing severe right heart dysfunction and heart failure. Pulmonary thromboendarterectomy (PTE) is the treatment of choice for CTEPH; however, this procedure is available not for all patients. Although the surgery performed in the conditions of centers with advanced experience generally shows good results, up to 40% of patients are technically inoperable or PTE is associated with a high risk of complications. At present, riociguat, the only officially approved drug from the class of soluble guanylate cyclase stimulators, is considered as a first-line treatment for inoperable and residual forms of STEPH. Introduction of riociguat to clinical practice can be called a real breakthrough in the treatment of patients with STEPH who cannot undergo PTE or those with relapse or persistent STEPH after the surgery.

scholarly journals Pharmacological therapy for patients with chronic thromboembolic pulmonary hypertension

2015 ◽  
Vol 24 (136) ◽  
pp. 272-282 ◽  
Author(s):  
Marius M. Hoeper
Keyword(s):  
Pulmonary Hypertension ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Phase Iii ◽  
Current Evidence ◽  
Endothelin Receptor ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Thromboembolic Pulmonary Hypertension ◽  
Soluble Guanylate Cyclase Stimulator

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but life-threatening disease resulting from unresolved thromboembolic obstructions. Pulmonary endarterectomy (PEA) surgery is the gold-standard treatment as it is potentially curative; however, not all patients are deemed operable and up to one-third have persistent or recurrent CTEPH after the procedure. Pulmonary arterial hypertension (PAH) and CTEPH have similar clinical presentations and histopathological features, so agents shown to be effective in PAH have often been prescribed to patients with CTEPH in the absence of proven therapies. However, clinical evidence for this strategy is not compelling. A number of small uncontrolled trials have investigated endothelin receptor antagonists, prostacyclin analogues and phosphodiesterase type 5 inhibitors in CTEPH with mixed results, and a phase III study of the endothelin receptor antagonist bosentan met only one of its two co-primary end-points. Recently, however, the soluble guanylate cyclase stimulator, riociguat, was approved in the USA and Europe for the treatment of inoperable or persistent/recurrent CTEPH following positive results from the phase III CHEST study (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial). This article reviews the current evidence for the use of pharmacological therapies in CTEPH.

scholarly journals Methods of Pharmacological Treatment of Chronic Thromboembolic Pulmonary Hypertension Current Approaches to the Patients Management

Kardiologiia ◽  
2018 ◽  
Vol 58 (11) ◽  
pp. 82-93
Author(s):  
E. A. Ushkalova ◽  
S. K. Zyryanov ◽  
K. E. Zatolochina
Keyword(s):  
Pulmonary Hypertension ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Vasculature ◽  
The European Union ◽  
Pulmonary Thromboendarterectomy ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Thromboembolic Pulmonary Hypertension ◽  
Phosphodiesterase Type

In this paper we have discussed epidemiology, pathogenesis, and approaches to treatment of chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH is a unique potentially curable form of pulmonary hypertension. The gold standard of CTEPH treatment is pulmonary thromboendarterectomy. However, about 40% of patients with CTEPH are inoperable due to distal surgically inaccessible lesions of the pulmonary vasculature, severe hemodynamic impairments, or other contraindications. In addition, nearly half of patients have persistent or recurrent pulmonary hypertension following surgery. Current guidelines support the use of pharmacotherapy in these patients. In the article we have presented results of main clinical studies of targeted drugs therapy (endothelin receptor antagonists, prostanoids, phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators) of patients with CTEPH. The only drug that has demonstrated robust clinical efficacy in terms of improvment hemodynamic parameters, exercise capacity and patients’ quality of life is the stimulator of the soluble guanylate cyclase riociguat. The efficacy and safety of riociguat have been investigated in short-term and long-term studies with follow-up up to 6 years. Results of these studies have constituted the basis forits approval by the regulatory authorities of more than 50 countries for the treatment of inoperable CTEPH and persistent or recurrent CTEPH after pulmonary thromboendarterectomy. In the European Union, USA and many other countries, riociguat is the only pharmacological agent approved for these indications.

scholarly journals Soluble Guanylate Cyclase Stimulators for Chronic Thromboembolic Pulmonary Hypertension Patients Treatment: New Data

2020 ◽  
Vol 16 (2) ◽  
pp. 317-323
Author(s):  
M. A. Simakova ◽  
O. M. Moiseeva
Keyword(s):  
Pulmonary Hypertension ◽  
Guanylate Cyclase ◽  
Safety Profile ◽  
Soluble Guanylate Cyclase ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Publication Date ◽  
Right Heart ◽  
Good Tolerability ◽  
Thromboembolic Pulmonary Hypertension ◽  
Positive Effect

This narrative review describes and appraises some relatively new studies investigating the efficacy and safety profile of soluble guanylate cyclase stimulator riociguat in patients suffering from pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). It has been a while since the publication date of pivotal CHEST-1 trial in 2013. New studies available complement existing evidence, expound on specific questions and open new frontiers for CTEPH investigations going forward. In this paper authors attempted to present data from post-hocanalysis of the CHEST-1 study and real-world data on riociguat treatment, confirming the positive effect of the drug on hemodynamic parameters of the pulmonary circulation and the functional status of patients. This effect was shown previously in large randomized trials. The extremely important positive effect of riociguat demonstrated both in the group of inoperable patients with CTEPH and in patients with residual pulmonary hypertension after pulmonary thrombendarterectomy. Of great interest are the presented some authors results of reverse remodelling of the right heart chambers during riociguat therapy in CTEPH patients, including using unique imaging methods (magnetic resonance imaging and positron emission tomography) to evaluate targeted medicinal therapy in terms of right heart remodelling. The safety profile of the drug was analyzed in the long-term post-registration international, multicenter, prospective, observational study EXPERT (NCT02092818), which confirmed the good tolerability and safety of riociguat therapy in PAH and CTEPH patients.

scholarly journals 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

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).

scholarly journals Chronic Thromboembolic Pulmonary Hypertension Medical Management

2021 ◽  
Vol 17 (2) ◽  
pp. e28-e32
Author(s):  
Ryan Logue ◽  
Zeenat Safdar
Keyword(s):  
Pulmonary Hypertension ◽  
Medical Management ◽  
Soluble Guanylate Cyclase ◽  
Pulmonary Arteries ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Standard Of Care ◽  
Pulmonary Angiography ◽  
Thromboembolic Pulmonary Hypertension ◽  
Soluble Guanylate Cyclase Stimulator

Chronic thromboembolic pulmonary hypertension (CTEPH) is a common long-term complication of pulmonary embolism characterized by thromboembolic obstruction of the pulmonary arteries, vascular arteriopathy, vascular remodeling, and ultimately pulmonary hypertension (PH). Although pulmonary endarterectomy (PEA) surgery is the standard of care, approximately 40% of patients in the international CTEPH registry were deemed inoperable. In addition to lifelong anticoagulation, the cornerstone of PH-specific medical management is riociguat, a soluble guanylate cyclase stimulator. Medical management should be started early in CTEPH patients and may be used as a bridge to PEA surgery or balloon pulmonary angiography. Medical management is indicated for inoperable CTEPH patients and patients who have recurrence of PH after PEA surgery.

scholarly journals Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2)

2014 ◽  
Vol 45 (5) ◽  
pp. 1293-1302 ◽  
Author(s):  
Gérald Simonneau ◽  
Andrea M. D’Armini ◽  
Hossein-Ardeschir Ghofrani ◽  
Friedrich Grimminger ◽  
Marius M. Hoeper ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Soluble Guanylate Cyclase ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Risk Profile ◽  
World Health ◽  
Walking Distance ◽  
Open Label ◽  
End Points ◽  
Thromboembolic Pulmonary Hypertension

Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of inoperable and persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). In the 16-week CHEST-1 study, riociguat showed a favourable benefit–risk profile and improved several clinically relevant end-points in patients with CTEPH. The CHEST-2 open-label extension evaluated the long-term safety and efficacy of riociguat.Eligible patients from CHEST-1 received riociguat individually adjusted up to a maximum dose of 2.5 mg three times daily. The primary objective was the safety and tolerability of riociguat; exploratory efficacy end-points included 6-min walking distance (6MWD) and World Health Organization (WHO) functional class (FC).Overall, 237 patients entered CHEST-2 and 211 (89%) were ongoing at this interim analysis (March 2013). The safety profile of riociguat in CHEST-2 was similar to CHEST-1, with no new safety signals. Improvements in 6MWD and WHO FC observed in CHEST-1 persisted for up to 1 year in CHEST-2. In the observed population at 1 year, mean±sd6MWD had changed by +51±62 m (n=172)versusCHEST-1 baseline (n=237), and WHO FC had improved/stabilised/worsened in 47/50/3% of patients (n=176)versusCHEST-1 baseline (n=236).Long-term riociguat had a favourable benefit–risk profile and apparently showed sustained benefits in exercise and functional capacity for up to 1 year.

scholarly journals The role of inflammation in a rat model of chronic thromboembolic pulmonary hypertension induced by carrageenan

2020 ◽  
Vol 8 (7) ◽  
pp. 492-492
Author(s):  
Dawen Wu ◽  
Yunfei Chen ◽  
Wenfeng Wang ◽  
Hongli Li ◽  
Minxia Yang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Rat Model ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Thromboembolic Pulmonary Hypertension
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