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 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 Surgical Treatment of Chronic Thromboembolic Pulmonary Hypertension

2007 ◽  
Vol 6 (2) ◽  
pp. 83-91
Author(s):  
Michael M. Madani ◽  
Stuart W. Jamieson
Keyword(s):  
Pulmonary Hypertension ◽  
Medical Management ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Thromboembolic Disease ◽  
Definitive Treatment ◽  
Pulmonary Vasculature ◽  
Pulmonary Thromboendarterectomy ◽  
Thromboembolic Pulmonary Hypertension ◽  
Long Term Prognosis

Pulmonary hypertension as the result of chronic pulmonary thromboembolic disease is a serious condition with poor long-term prognosis. The condition is one of the more common cardiovascular diseases affecting Americans, yet it is severely underdiagnosed. Pulmonary thromboendarterectomy is the definitive treatment for chronic pulmonary hyper-tension as the result of thromboembolic disease; however. it is an uncommon procedure, primarily because of lack of recognition on the part of the clinicians. Patients affected by chronic thromboembolic pulmonary hypertension (CTEPH) may present with a variety of debilitating cardiopulmonary symptoms. However, once diagnosed, there is no curative role for medical management, and surgery remains the only option. Palliation therapy with medical management in order to delay surgery carries the risk of prolonging the disease and irreversibly damaging unaffected pulmonary vasculature.

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.

Medical Therapy for Chronic Thromboembolic Pulmonary Hypertension

2014 ◽  
Vol 12 (4) ◽  
pp. 193-198 ◽  
Author(s):  
Josanna Rodriguez-Lopez ◽  
Richard N. Channick
Keyword(s):  
Pulmonary Hypertension ◽  
Medical Therapy ◽  
Soluble Guanylate Cyclase ◽  
Significant Proportion ◽  
Pulmonary Arteries ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Thromboendarterectomy ◽  
Specialized Center ◽  
Thromboembolic Pulmonary Hypertension ◽  
Recent Phase

Chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary hypertension (PH) secondary to chronic emboli, obstructing the pulmonary arteries. This results in increased pulmonary vascular resistance and right ventricular failure. CTEPH is the only form of PH that is potentially curable, through a surgical procedure that removes the chronic emboli: pulmonary thromboendarterectomy (PTE). The first step in managing patients diagnosed with CTEPH is to determine if they are operable. The use of medical therapy should never delay referral for surgery, which should be done at a specialized center with expertise in CTEPH. Since a significant proportion of CTEPH patients are not surgical candidates, or are among the 10% to 15% of patients that have persistent or recurrent PH after surgery, there is a need for effective medical therapy. The use of several pulmonary arterial hypertension (PAH)-targeted agents have been studied, mostly in small uncontrolled trials. A recent Phase 3 clinical trial found riociguat, a stimulator of soluble guanylate cyclase (sGC), to be effective for inoperable CTEPH.

scholarly journals Revisiting a Distinct Entity in Pulmonary Vascular Disease: Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 355
Author(s):  
Munish Sharma ◽  
Deborah Jo Levine
Keyword(s):  
Pulmonary Hypertension ◽  
Medical Therapy ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Progressive Increase ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Pulmonary Thromboendarterectomy ◽  
Percutaneous Balloon ◽  
Definitive Therapy ◽  
Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a specific type of pulmonary hypertension (PH) and the major component of Group 4 pulmonary hypertension (PH). It is caused by pulmonary vasculature obstruction that leads to a progressive increase in pulmonary vascular resistance and, ultimately, to failure of the right ventricle. Pulmonary thromboendarterectomy (PEA) is the only definitive therapy, so a timely diagnosis and early referral to a specialized PEA center to determine candidacy is prudent for a favorable outcome. Percutaneous balloon pulmonary angioplasty (BPA) has a potential role in patients unsuitable for PEA. Medical therapy with riociguat is the only PH-specific medical therapy currently approved for the treatment of inoperable or persistent CTEPH. This review article aims to revisit CTEPH succinctly with a review of prevailing literature.

scholarly journals EXPRESS: Evolution of randomized, controlled studies of medical therapy in chronic thromboembolic pulmonary hypertension

2021 ◽  
pp. 204589402110073
Author(s):  
Nick H Kim ◽  
Demosthenes G. Papamatheakis ◽  
Timothy M. Fernandes
Keyword(s):  
Pulmonary Hypertension ◽  
Medical Therapy ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Controlled Study ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Randomized Controlled ◽  
Randomized Controlled Studies ◽  
Need To Evaluate ◽  
Thromboembolic Pulmonary Hypertension ◽  
Phosphodiesterase Type

Although pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH), many patients have inoperable disease, and some have persistent or recurrent pulmonary hypertension (PH) after surgery. Alternative options (balloon pulmonary angioplasty [BPA] and PH-targeted medical therapy) are, therefore, required. Studies of medical therapies for CTEPH have evolved since AIR, the first randomized, controlled study of a PH-targeted therapy (inhaled iloprost) to include patients with CTEPH. Key learnings from these studies include the need to evaluate CTEPH separately from other types of PH, the importance of prospective operability adjudication as part of the protocol, and the need for sufficient duration to allow treatment benefits to become apparent. The 16-week CHEST-1 study was the first to operationalize these learnings, demonstrating a significant mean improvement in 6-minute walk distance (+46 m) and improvements in hemodynamic endpoints with riociguat versus placebo. Findings from previous studies will inform the design of future studies to address key issues related to combination medical therapy. Data on combinations of macitentan with phosphodiesterase type 5 inhibitors or oral prostanoids are available from MERIT, the first study to allow such regimens. No data on combinations including riociguat, the only licensed medical therapy for CTEPH, are available. Studies are also needed for multi-modality treatment, including medical therapy plus BPA, and medical therapy as a bridge to PEA in selected operable patients. To address these issues and improve patient outcomes, it is vital that we learn from current studies to improve future trial design.

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 Phosphodiesterase type 5 inhibitor to riociguat transition is associated with hemodynamic and symptomatic improvement in pulmonary hypertension

2017 ◽  
Vol 7 (2) ◽  
pp. 539-542 ◽  
Author(s):  
Ryan Davey ◽  
Raymond L. Benza ◽  
Srinivas Murali ◽  
Amresh Raina
Keyword(s):  
Pulmonary Hypertension ◽  
Soluble Guanylate Cyclase ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Symptomatic Improvement ◽  
Functional Class ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Thromboembolic Pulmonary Hypertension ◽  
Soluble Guanylate Cyclase Stimulator ◽  
Pulmonary Arterial ◽  
Phosphodiesterase Type

Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. We studied the clinical and hemodynamics effects of transitioning 12 pulmonary hypertension patients from Phosphodiesterase type 5 inhibitor (PDE5i) to riociguat, and demonstrated a significant increase in cardiac index, fall in pulmonary vascular resistance, and improvement in functional class with this switch. Switch from PDE5i to riociguat appeared to be safe and fairly well tolerated in most patients.

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