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Riociguat

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https://www.readbyqxmd.com/read/28513869/transition-of-intravenous-treprostinil-to-oral-therapy-in-a-patient-with-functional-class-iv-chronic-thromboembolic-pulmonary-hypertension
#1
Kristina M Thurber, Breann M Williams, Ruth E Bates, Robert P Frantz
Chronic thromboembolic pulmonary hypertension (CTEPH) occurs when pulmonary emboli fail to resolve with anticoagulation. For patients with inoperable or residual CTEPH, riociguat is currently the only therapy approved by the United States Food and Drug Administration. However, some patients with CTEPH may require therapy beyond riociguat, such as intravenous prostacyclins, which can present significant administration challenges in patients with complex comorbid conditions. We describe a 42-year-old man with T12 paraplegia complicated by CTEPH (functional class IV with substantial right ventricular dysfunction) and severe pressure ulcers...
May 17, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28458514/riociguat-a-soluble-guanylate-cyclase-stimulator-for-the-treatment-of-pulmonary-hypertension
#2
REVIEW
Tian-Yu Lian, Xin Jiang, Zhi-Cheng Jing
Despite advances in treatments and improved survival, patients with pulmonary hypertension still experience poor exercise and functional capacity, which has a significant detrimental impact on their quality of life. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine 3',5'-monophosphate (cGMP) pathway has been shown to play an important role in cardiovascular physiology, especially in vasodilation and pulmonary vascular tone. The oral sGC stimulator riociguat has a dual mode of action on the NO-sGC-cGMP pathway: direct stimulation of sGC independent of NO and indirect simulation via sensitization of sGC to endogenous NO...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28356406/balloon-pulmonary-angioplasty-in-chronic-thromboembolic-pulmonary-hypertension
#3
REVIEW
Irene Lang, Bernhard C Meyer, Takeshi Ogo, Hiromi Matsubara, Marcin Kurzyna, Hossein-Ardeschir Ghofrani, Eckhard Mayer, Philippe Brenot
Chronic thromboembolic pulmonary hypertension (CTEPH) is thought to result from incomplete resolution of pulmonary thromboemboli that undergo organisation into fibrous tissue within pulmonary arterial branches, filling pulmonary arterial lumina with collagenous obstructions. The treatment of choice is pulmonary endarterectomy (PEA) in CTEPH centres, which has low post-operative mortality and good long-term survival. For patients ineligible for PEA or who have recurrent or persistent pulmonary hypertension after surgery, medical treatment with riociguat is beneficial...
March 31, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28356404/medical-management-of-chronic-thromboembolic-pulmonary-hypertension
#4
REVIEW
Joanna Pepke-Zaba, Hossein-Ardeschir Ghofrani, Marius M Hoeper
Chronic thromboembolic pulmonary hypertension (CTEPH) results from incomplete resolution of acute pulmonary emboli, organised into fibrotic material that obstructs large pulmonary arteries, and distal small-vessel arteriopathy. Pulmonary endarterectomy (PEA) is the treatment of choice for eligible patients with CTEPH; in expert centres, PEA has low in-hospital mortality rates and excellent long-term survival. Supportive medical therapy consists of lifelong anticoagulation plus diuretics and oxygen, as needed...
March 31, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28289495/treatment-of-chronic-thromboembolic-pulmonary-hypertension-the-role-of-medical-therapy-and-balloon-pulmonary-angioplasty
#5
Timothy M Fernandes, David S Poch, William R Auger
Chronic thromboembolic pulmonary hypertension (CTEPH) is a potentially curable disease when treated with pulmonary thromboendarterectomy (PTE). However, even at experienced surgical centers, nearly one-third of patients with CTEPH will be deemed inoperable for reasons including distal disease, comorbidities, or out-of-proportion pulmonary hypertension. It is in these patients with inoperable CTEPH that pulmonary hypertension (PH)-targeted medical therapy and balloon pulmonary angioplasty have potential therapeutic value...
October 2016: Methodist DeBakey Cardiovascular Journal
https://www.readbyqxmd.com/read/28190787/comparison-of-hemodynamic-parameters-in-treatment-na%C3%A3-ve-and-pre-treated-patients-with-pulmonary-arterial-hypertension-in-the-randomized-phase-iii-patent-1-study
#6
Nazzareno Galiè, Friedrich Grimminger, Ekkehard Grünig, Marius M Hoeper, Marc Humbert, Zhi-Cheng Jing, Anne M Keogh, David Langleben, Lewis J Rubin, Arno Fritsch, Neil Davie, Hossein-Ardeschir Ghofrani
BACKGROUND: Detailed hemodynamic data from the phase III PATENT-1 study of riociguat in patients with pulmonary arterial hypertension (PAH) were investigated. METHODS: Patients with PAH who were treatment naïve or pre-treated with endothelin receptor antagonists or non-intravenous prostanoids were randomly assigned to riociguat up to 2.5 mg 3 times a day or placebo. Hemodynamic parameters were assessed at baseline and week 12. RESULTS: Riociguat significantly decreased pulmonary vascular resistance in treatment-naïve (n = 221; least squares [LS] mean difference -266 dyne∙sec∙cm(-5) [95% confidence interval (CI) -357 to -175; p < 0...
May 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28025101/soluble-guanylate-cyclase-stimulators-increase-sensitivity-to-cisplatin-in-head-and-neck-squamous-cell-carcinoma-cells
#7
Traci R Tuttle, Vinita Takiar, Bhavna Kumar, Pawan Kumar, Nira Ben-Jonathan
Head and neck squamous cell carcinoma (HNSCC) is an aggressive and often fatal disease. Cisplatin is the most common chemotherapeutic drug in the treatment of HNSCC, but intrinsic and acquired resistance are frequent, and severe side effects occur at high doses. The second messenger cyclic GMP (cGMP) is produced by soluble guanylate cyclase (sGC). We previously reported that activation of the cGMP signaling cascade caused apoptosis in HNSCC cells, while others found that this pathway enhances cisplatin efficacy in some cell types...
March 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28011757/haemodynamic-effects-of-riociguat-in-inoperable-recurrent-chronic-thromboembolic-pulmonary-hypertension
#8
Nick H Kim, Andrea M D'Armini, Friedrich Grimminger, Ekkehard Grünig, Marius M Hoeper, Pavel Jansa, Eckhard Mayer, Claus Neurohr, Gérald Simonneau, Adam Torbicki, Chen Wang, Arno Fritsch, Neil Davie, Hossein-Ardeschir Ghofrani
OBJECTIVE: We compared the haemodynamic effects of riociguat in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent CTEPH after pulmonary endarterectomy in the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial 1 study. METHODS: Patients with inoperable or persistent/recurrent CTEPH (n=261; mean± SD age 59±14 years; 66% women) were randomised to riociguat (up to 2.5 mg three times daily) or placebo...
April 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/27990270/recent-advances-in-the-management-of-pulmonary-arterial-hypertension
#9
REVIEW
Halley Tsai, Yon K Sung, Vinicio de Jesus Perez
Over the past 20 years, there has been an explosion in the development of therapeutics to treat pulmonary arterial hypertension (PAH), a rare but life-threatening disorder associated with progressive elevation of pulmonary pressures and severe right heart failure. Recently, the field has seen the introduction of riociguat, a soluble guanylate cyclase stimulator, a new endothelin receptor antagonist (macitentan), and oral prostanoids (treprostinil and selexipag). Besides new drugs, there have been significant advances in defining the role of upfront combination therapy in treatment-naïve patients as well as proposed methods to deliver systemic prostanoids by use of implantable pumps...
2016: F1000Research
https://www.readbyqxmd.com/read/27942445/combination-therapy-with-riociquat-and-inhaled-treprostinil-in-inoperable-and-progressive-chronic-thromboembolic-pulmonary-hypertension
#10
John W Swisher, Dillon Elliott
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by formation of chronic, organized thrombus in pulmonary arteries resulting in development of pulmonary hypertension. We describe the favorable recovery of a patient with inoperable CTEPH treated with combination riociguat and inhaled treprostinil. The patient is a 77 year old female who presented with bilateral pulmonary emboli and was anticoagulated with warfarin for six months. One year later the patient developed recurrent dyspnea and multiple bilateral pulmonary emboli were again noted...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/27900610/novel-sgc-stimulators-and-sgc-activators-for-the-treatment-of-heart-failure
#11
Stefanie Breitenstein, Lothar Roessig, Peter Sandner, Kelly S Lewis
The burden of heart failure (HF) increases worldwide with an aging population, and there is a high unmet medical need in both, heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). The nitric oxide (NO) pathway is a key regulator in the cardiovascular system and modulates vascular tone and myocardial performance. Disruption of the NO-cyclic guanosine monophosphate (cGMP) signaling axis and impaired cGMP formation by endothelial dysfunction could lead to vasotone dysregulation, vascular and ventricular stiffening, fibrosis, and hypertrophy resulting in a decline of heart as well as kidney function...
November 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27899043/use-of-biologics-and-other-novel-therapies-for-the-treatment-of-systemic-sclerosis
#12
Cosimo Bruni, Emanuela Praino, Yannick Allanore, Oliver Distler, Armando Gabrielli, Florenzo Iannone, Marco Matucci-Cerinic
Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by vasculopathy, inflammation and fibrosis. These three main disease-determining pathways are the target of the currently available treatments used to possibly modify the progression of disease-related manifestations, although this synergy has not been fully applied on SSc joint, skin or lung involvement yet. Areas covered: we describe the current status of SSc treatment/therapy performing a literature search in MEDLINE/Pubmed and Thomson Reuter's Web of Science for articles published until March 2016...
December 12, 2016: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/27890471/rationale-and-study-design-of-motion-a-phase-4-prospective-single-arm-open-label-study-to-measure-outcomes-in-patients-with-pulmonary-arterial-hypertension-not-on-active-treatment
#13
Stephen C Mathai, Omar Minai, Sean D Sullivan, Debra Lerner, Deborah Levine
In clinical trials of treatments for pulmonary arterial hypertension (PAH), objective measures, such as 6-min walking distance (6MWD) are limited in their ability to characterize the impact of PAH therapy from a patient's perspective. Few clinical studies have evaluated the primary effects of pharmacologic treatment on patient-reported outcomes, such as symptoms, health-related quality of life (HRQoL), and productivity. MOTION (NCT02191137) is a prospective, multicenter, single-arm, open-label, phase 4 trial designed to assess whether riociguat monotherapy will improve patient-reported outcomes in patients with PAH in the United States who are not currently on treatment...
November 2, 2016: Respiratory Medicine
https://www.readbyqxmd.com/read/27890470/sgc-stimulators-evidence-for-riociguat-beyond-groups-1-and-4-pulmonary-hypertension
#14
Raymond Benza, Stephen Mathai, Steven D Nathan
Pulmonary hypertension (PH) is a chronic cardiopulmonary disorder that if left untreated, progresses rapidly and is ultimately fatal. The World Health Organization (WHO) has classified PH into 5 distinct groups according to pathophysiology, hemodynamic characteristics, and clinical presentation. Dysfunction in the nitric oxide (NO) pathway plays a key role in the pulmonary hypertension disease process, including in WHO Groups 2 and 3 PH. PH is associated with endothelial dysfunction, impaired synthesis of NO, and insufficient stimulation of the NO-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway, which reduces cGMP production...
November 14, 2016: Respiratory Medicine
https://www.readbyqxmd.com/read/27887774/rationale-and-study-design-of-respite-an-open-label-phase-3b-study-of-riociguat-in-patients-with-pulmonary-arterial-hypertension-who-demonstrate-an-insufficient-response-to-treatment-with-phosphodiesterase-5-inhibitors
#15
Marius M Hoeper, James R Klinger, Raymond L Benza, Gerald Simonneau, David Langleben, Robert Naeije, Paul A Corris
Patients with pulmonary arterial hypertension (PAH) who do not have an adequate response to therapy with phosphodiesterase-5 inhibitors (PDE-5i) may have insufficient synthesis of cyclic guanosine monophosphate (cGMP). These patients may respond to a direct soluble guanylate cyclase (sGC) stimulator such as riociguat. RESPITE (NCT02007629) was an open-label, multicenter, uncontrolled, single-arm phase 3b study of riociguat in patients with PAH who demonstrated an insufficient response to treatment with PDE-5i...
November 5, 2016: Respiratory Medicine
https://www.readbyqxmd.com/read/27824545/targeted-therapy-in-systemic-sclerosis
#16
REVIEW
Murray Baron
Targeted therapies use an understanding of the pathophysiology of a disease in an individual patient. Although targeted therapy for systemic sclerosis (SSc, scleroderma) has not yet reached the level of patient-specific treatments, recent developments in the understanding of the global pathophysiology of the disease have led to new treatments based on the cells and pathways that have been shown to be involved in the disease pathogenesis. The presence of a B cell signature in skin biopsies has led to the trial of rituximab, an anti-CD20 antibody, in SSc...
October 31, 2016: Rambam Maimonides Medical Journal
https://www.readbyqxmd.com/read/27750459/riociguat-for-the-treatment-of-pulmonary-hypertension-a-safety-evaluation
#17
REVIEW
Christina Binder, Caroline Zotter-Tufaro, Diana Bonderman
The development of pulmonary hypertension (PH) has multifactorial underlying pathophysiological causes and can be classified into five groups. While three different classes of therapeutic drugs are licensed for the treatment of pulmonary arterial hypertension (PAH, WHO group 1), specific medical therapies are lacking for other forms of PH, such as PH due to left heart disease. In 2013 riociguat, a first-in class soluble guanylate cyclase stimulator, has also become available for the treatment of PAH. Riociguat was further introduced as the first approved pharmacotherapy for the treatment of patients with chronic thromboembolic PH (WHO group 4, CTEPH)...
December 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27746061/rise-ssc-riociguat-in-diffuse-cutaneous-systemic-sclerosis
#18
Oliver Distler, Janet Pope, Chris Denton, Yannick Allanore, Marco Matucci-Cerinic, Janethe de Oliveira Pena, Dinesh Khanna
RISE-SSc is a randomized, double-blind, placebo-controlled phase 2 study investigating the efficacy and safety of riociguat in patients with diffuse cutaneous systemic sclerosis (dcSSc). Based on positive results from riociguat trials in patients with pulmonary hypertension and chronic thromboembolic pulmonary hypertension in combination with the known antiproliferative and antifibrotic effects seen in animal models, patients with SSc may benefit from treatment with riociguat. Patients with SSc meeting the ACR/EULAR systemic sclerosis classification criteria with diffuse cutaneous SSc (dcSSc) subset per LeRoy criteria, and a disease duration of less than or equal to 18 months will be randomized to placebo or riociguat 0...
January 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/27627939/update-on-pharmacotherapy-for-pulmonary-hypertension
#19
REVIEW
David L Prior, Heath Adams, Trevor J Williams
Pulmonary arterial hypertension (PAH) is a rare disease with a poor prognosis if not treated. Pharmacological treatment options for PAH have increased significantly over the past 10 years, with availability of intravenous, oral and inhaled drugs targeting the nitric oxide, endothelin and prostacyclin pathways. Treatment with these therapies in specialised pulmonary hypertension centres has resulted in reductions in patient symptoms, disease progression and mortality, and improved exercise capacity. Recognition of chronic thromboembolic pulmonary hypertension is important, as this cause of pulmonary hypertension may be amenable to surgical treatment...
September 19, 2016: Medical Journal of Australia
https://www.readbyqxmd.com/read/27615023/comparative-effectiveness-of-pharmacologic-interventions-for-pulmonary-arterial-hypertension-a-systematic-review-and-network-meta-analysis
#20
REVIEW
Snigdha Jain, Rohan Khera, Saket Girotra, David Badesch, Zhen Wang, Mohammad Hassan Murad, Amy Blevins, Gregory A Schmidt, Siddharth Singh, Alicia K Gerke
BACKGROUND: We conducted a systematic review and network meta-analysis to examine comparative efficacy and tolerability of pharmacologic interventions for pulmonary arterial hypertension (PAH). METHODS: MEDLINE, the Cochrane Register, EMBASE, CINAHL, and clinicaltrials.gov were searched (January 1, 1990 to March 3, 2016). Randomized controlled trials (RCTs) studying the approved pharmacologic agents endothelin receptor antagonists (ERA), phosphodiesterase inhibitors (PDE5i), the oral/inhaled (PO/INH) and IV/subcutaneous (SC) prostanoids, and riociguat and selexipag, alone or in combination, for pulmonary arterial hypertension (PAH) and reporting at least one efficacy outcome were selected...
January 2017: Chest
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