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https://www.readbyqxmd.com/read/27900610/novel-sgc-stimulators-and-sgc-activators-for-the-treatment-of-heart-failure
#1
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
#2
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...
November 30, 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
#3
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
#4
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
#5
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
#6
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
#7
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)...
November 9, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27746061/rise-ssc-riociguat-in-diffuse-cutaneous-systemic-sclerosis
#8
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...
September 28, 2016: Respiratory Medicine
https://www.readbyqxmd.com/read/27627939/update-on-pharmacotherapy-for-pulmonary-hypertension
#9
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-pharmacological-interventions-for-pulmonary-arterial-hypertension-a-systematic-review-and-network-meta-analysis
#10
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 pharmacological interventions for pulmonary arterial hypertension (PAH). METHODS: MEDLINE, Cochrane register, EMBASE, CINAHL and clinicaltrials.gov were searched (January 1, 1990 - March 3, 2016). Randomized controlled trials (RCTs) of approved pharmacological agents - endothelin receptor antagonists (ERA), phosphodiesterase inhibitors (PDE5i), oral/inhaled and intravenous/subcutaneous prostanoids, riociguat, and selexipag, alone or in combination for pulmonary arterial hypertension (PAH) reporting at least one efficacy outcome were selected...
September 8, 2016: Chest
https://www.readbyqxmd.com/read/27590259/evaluation-of-the-pharmacodynamic-effects-of-riociguat-in-subjects-with-pulmonary-hypertension-and-heart-failure-with-preserved-ejection-fraction-study-protocol-for-a%C3%A2-randomized-controlled-trial
#11
Julia Mascherbauer, Ekkehard Grünig, Michael Halank, Wolfgang Hohenforst-Schmidt, Andreas A Kammerlander, Ingrid Pretsch, Regina Steringer-Mascherbauer, Silvia Ulrich, Irene M Lang, Manfred Wargenau, Reiner Frey, Diana Bonderman
BACKGROUND: The presence of pulmonary hypertension (PH) severely aggravates the clinical course of heart failure with preserved ejection fraction (HFPEF) resulting in substantial morbidity and mortality. So far, neither established heart failure therapies nor pulmonary vasodilators have proven to be effective for this condition. Riociguat (Adempas®, BAY 63-2521), a stimulator of soluble guanylate cyclase, is a novel pulmonary and systemic vasodilator that has been approved for the treatment of precapillary forms of PH...
September 2, 2016: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/27571006/medical-therapy-in-chronic-thromboembolic-pulmonary-hypertension
#12
Joanna Pepke-Zaba, Xavier Jais, Richard Channick
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but life-threatening condition resulting from unresolved thromboembolic obstructions. Pulmonary endarterectomy surgery is currently the standard of treatment, as it is potentially curative; however, not all cases are amenable to surgical intervention due to distal distribution of the organized thromboembolic material or the presence of comorbidities. Up to one-third of patients have persistent or recurrent pulmonary hypertension after pulmonary endarterectomy...
July 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27492004/-pulmonary-hypertension-what-is-new-in-therapy
#13
N Sommer, M Hecker, K Tello, M Richter, C Liebetrau, M A Weigand, W Seeger, A Ghofrani, H Gall
Pulmonary hypertension (PH) comprises a group of pulmonary vascular diseases that are characterized by progressive exertional dyspnea and right heart insufficiency ultimately resulting in right heart decompensation. The classification is into five clinical subgroups that form the absolutely essential basis for decisions on the indications for different pharmacological and non-pharmacological forms of treatment. The guidelines were updated in 2015 and in addition to the hitherto existing pharmacological treatment options of phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostacyclins, the soluble guanylate cyclase stimulator riociguat has now been incorporated for treatment of certain forms of PH...
August 2016: Der Anaesthesist
https://www.readbyqxmd.com/read/27457511/riociguat-for-the-treatment-of-pulmonary-arterial-hypertension-associated-with-connective-tissue-disease-results-from-patent-1-and-patent-2
#14
Marc Humbert, J Gerry Coghlan, Hossein-Ardeschir Ghofrani, Friedrich Grimminger, Jian-Guo He, Gabriela Riemekasten, Carmine Dario Vizza, Annette Boeckenhoff, Christian Meier, Janethe de Oliveira Pena, Christopher P Denton
BACKGROUND: The 12-week, phase III Pulmonary Arterial hyperTENsion sGC-stimulator Trial (PATENT)-1 study investigated riociguat in patients with pulmonary arterial hypertension (PAH). Here, we present a prospectively planned analysis of the safety and efficacy of riociguat in the subgroup of patients with PAH associated with connective tissue disease (PAH-CTD). METHODS: Patients with PAH-CTD were further classified post hoc as having PAH associated with systemic sclerosis or PAH-other defined CTD...
July 25, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27404679/amelioration-of-right-ventricular-function-after-hybrid-therapy-with-riociguat-and-balloon-pulmonary-angioplasty-in-patients-with-chronic-thromboembolic-pulmonary-hypertension
#15
EDITORIAL
Toshimitsu Tsugu, Mitsushige Murata, Takashi Kawakami, Masaharu Kataoka, Yuji Nagatomo, Hikaru Tsuruta, Yuji Itabashi, Yuichiro Maekawa, Keiichi Fukuda
No abstract text is available yet for this article.
October 15, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27364190/computational-exploration-of-the-binding-mode-of-heme-dependent-stimulators-into-the-active-catalytic-domain-of-soluble-guanylate-cyclase
#16
Luis Agulló, Ignasi Buch, Hugo Gutiérrez-de-Terán, David Garcia-Dorado, Jordi Villà-Freixa
Soluble guanylate cyclase (sGC), the main target of nitric oxide (NO), has been proven to have a significant role in coronary artery disease, pulmonary hypertension, erectile dysfunction, and myocardial infarction. One of its agonists, BAY 41-2272 (Riociguat), has been recently approved for treatment of pulmonary arterial hypertension (PHA), while some others are in clinical phases of development. However, the location of the binding sites for the two known types of agonists, heme-dependent stimulators and heme-independent activators, is a matter of debate, particularly for the first group where both a location on the regulatory (H-NOX) and on the catalytic domain have been suggested by different authors...
October 2016: Proteins
https://www.readbyqxmd.com/read/27354811/treatment-of-patients-with-chronic-thrombo-embolic-pulmonary-hypertension-focus-on-riociguat
#17
REVIEW
Zachary R Smith, Charles T Makowski, Rana L Awdish
Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease of the pulmonary vascular bed that is characterized by elevations in the mean pulmonary artery pressure in the setting of perfusion defects on ventilation-perfusion scan, and subsequently confirmed by pulmonary angiography. CTEPH, or World Health Organization (WHO) group 4 pulmonary hypertension, is a result of unresolved thromboembolic obstruction in the pulmonary arteries. Pulmonary endarterectomy (PEA) is the treatment of choice for CTEPH as it is a potentially curative therapy...
2016: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/27326239/riociguat-for-the-treatment-of-pulmonary-hypertension-chinese-subgroup-analyses-and-comparison
#18
Chen Wang, Zhi-Cheng Jing, Yi-Gao Huang, Da-Xin Zhou, Zhi-Hong Liu, Christian Meier, Sylvia Nikkho, John Curram, Peng Zhang, Jian-Guo He
OBJECTIVE: PATENT-1 and CHEST-1 were pivotal, international phase III trials assessing riociguat for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Here we compare Chinese patients from these studies with the overall populations, and report the clinical effect and safety of riociguat in Chinese patients with PAH and CTEPH. METHODS: PATENT-1 was a 12-week, randomised, double-blind, placebo-controlled trial of riociguat (maximum 2...
2016: Heart Asia
https://www.readbyqxmd.com/read/27263466/riociguat-mode-of-action-and-clinical-development-in-pulmonary-hypertension
#19
Hossein-Ardeschir Ghofrani, Marc Humbert, David Langleben, Ralph Schermuly, Johannes-Peter Stasch, Martin R Wilkins, James R Klinger
Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive and debilitating diseases characterized by gradual obstruction of the pulmonary vasculature, leading to elevated pulmonary artery pressure and increased pulmonary vascular resistance. If untreated, they can result in death due to right heart failure. Riociguat is a novel soluble guanylate cyclase (sGC) stimulator that is approved for the treatment of PAH and CTEPH. Here we describe in detail the role of the nitric oxide-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway in the pathogenesis of PAH and CTEPH, and the mode of action of riociguat...
June 2, 2016: Chest
https://www.readbyqxmd.com/read/27228047/riociguat-for-pulmonary-hypertension
#20
David Pitonzo, Mark E Archambault
Riociguat is newly approved by the FDA for treatment of patients with groups 1 or 4 pulmonary hypertension. Although several vasodilators are on the market for the treatment of pulmonary hypertension group 1, none have been shown to be invariably effective in the treatment of chronic thromboembolic pulmonary hypertension.
June 2016: JAAPA: Official Journal of the American Academy of Physician Assistants
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