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https://www.readbyqxmd.com/read/29738821/discovery-and-development-of-sgc-stimulators-for-the-treatment-of-pulmonary-hypertension-and-rare-diseases
#1
REVIEW
Peter Sandner, Eva-Maria Becker-Pelster, Johannes Peter Stasch
The NO/sGC/cGMP signaling cascade plays a pivotal role in regulation of cardiovascular, cardiopulmonary and cardiorenal diseases and impairment of this cascade results in severe pathologies. Therefore, pharmacological interventions, targeting this pathway are promising strategies for treating a variety of diseases. Nitrates, supplementing NO and, PDE5 inhibitors preventing cGMP degradation, are used for angina pectoris treatment and the treatment of pulmonary arterial hypertension (PAH), respectively. More recently, a new class of drugs which directly stimulate the sGC enzyme and trigger NO-independent cGMP production was introduced and termed sGC stimulators...
May 5, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29623530/novel-insights-and-treatment-strategies-for-right-heart-failure
#2
REVIEW
Weiqin Lin, Ai-Ling Poh, W H Wilson Tang
PURPOSE OF REVIEW: The function of the right ventricle (RV) is intimately linked to its preload (systemic volume status) and afterload (pulmonary vasculature). In this review, we explore current knowledge in RV physiology, RV function assessment, causes of right heart failure (RHF), and specific treatment strategies for RHF. RECENT FINDINGS: We examine the evidence behind new pharmacological therapies available, such as macitentan and riociguat in the treatment of specific etiologies of RHF...
April 6, 2018: Current Heart Failure Reports
https://www.readbyqxmd.com/read/29616325/correction-to-real-world-switching-to-riociguat-management-and-practicalities-in-patients-with-pah-and-cteph
#3
Henning Gall, Jean-Luc Vachiéry, Nobuhiro Tanabe, Michael Halank, Mauricio Orozco-Levi, Lisa Mielniczuk, MiKyung Chang, Kai Vogtländer, Ekkehard Grünig
The original version of this article unfortunately contained a mistake. In the "Results" section, the percentage of patients with inoperable or persistent/recurrent CTEPH included in the study was reported as 85%. This has been corrected to 68% with this erratum.
April 3, 2018: Lung
https://www.readbyqxmd.com/read/29604206/from-molecules-to-patients-exploring-the-therapeutic-role-of-soluble-guanylate-cyclase-stimulators
#4
Peter Sandner
Nitric Oxide (NO) signaling represents one of the major regulatory pathways for cardiovascular function. After the discovery of NO, awarded with the Nobel Prize in 1998, this signaling cascade was stepwise clarified. We now have a good understanding of NO production and NO downstream targets such as the soluble guanylyl cyclases (sGCs) which catalyze cGMP production. Based on the important role of NO-signaling in the cardiovascular system, intense research and development efforts are currently ongoing to fully exploit the therapeutic potential of cGMP increase...
March 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29580746/reveal-risk-score-in-patients-with-chronic-thromboembolic-pulmonary-hypertension-receiving-riociguat
#5
Raymond L Benza, Harrison W Farber, Adaani Frost, Ekkehard Grünig, Marius M Hoeper, Dennis Busse, Christian Meier, Sylvia Nikkho, Hossein-Ardeschir Ghofrani
BACKGROUND: The REVEAL risk score (RRS) was developed to predict survival in patients with pulmonary arterial hypertension (PAH), based on multiple patient characteristics. Herein we calculated RRS for patients in the randomized CHEST-1 study and open-label CHEST-2 extension study of riociguat in inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). We investigated the effect of riociguat vs placebo on RRS in the CHEST-1 study, and the relationship between RRS and long-term outcomes in the CHEST-2 study...
March 1, 2018: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29565224/express-riociguat-treatment-for-portopulmonary-hypertension-a-subgroup-analysis-from-the-patent-1-2-studies
#6
Rodrigo Cartin-Ceba, Michael Halank, Ardeschir Ghofrani, Marc Humbert, John Mattson, Arno Fritsch, Michael Krowka
No abstract text is available yet for this article.
January 1, 2018: Pulmonary Circulation
https://www.readbyqxmd.com/read/29550521/effects-of-the-no-soluble-guanylate-cyclase-cgmp-system-on-the-functions-of-human-platelets
#7
REVIEW
Stephanie Makhoul, Elena Walter, Oliver Pagel, Ulrich Walter, Albert Sickmann, Stepan Gambaryan, Albert Smolenski, René P Zahedi, Kerstin Jurk
Platelets are circulating sentinels of vascular integrity and are activated, inhibited, or modulated by multiple hormones, vasoactive substances or drugs. Endothelium- or drug-derived NO strongly inhibits platelet activation via activation of the soluble guanylate cyclase (sGC) and cGMP elevation, often in synergy with cAMP-elevation by prostacyclin. However, the molecular mechanisms and diversity of cGMP effects in platelets are poorly understood and sometimes controversial. Recently, we established the quantitative human platelet proteome, the iloprost/prostacyclin/cAMP/protein kinase A (PKA)-regulated phosphoproteome, and the interactions of the ADP- and iloprost/prostacyclin-affected phosphoproteome...
March 14, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29545265/drugs-and-their-names
#8
(no author information available yet)
Over recent years, drug names have become more complex and difficult to pronounce (e.g. axicabtagene ciloleucel, ▼rurioctocog alfa pegol, ▼riociguat ).1,2 Although some rules underpin drug nomenclature, there are several examples of drugs with similar sounding names that are easily confused. In addition, the different levels of nomenclature (chemical, generic and brand names) may cause confusion for patients. Here, we provide an overview of how drugs get their names, the patterns that can be seen in naming conventions and highlight the risk associated with drugs with similar looking or similar sounding names...
March 2018: Drug and Therapeutics Bulletin
https://www.readbyqxmd.com/read/29526325/prevention-and-treatment-of-the-chronic-thromboembolic-pulmonary-hypertension
#9
Raffaele Pesavento, Paolo Prandoni
Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon and late complication of pulmonary embolism resulting from misguided remodelling of residual pulmonary thromboembolic material and small-vessel arteriopathy. CTEPH is the only form of pulmonary hypertension (PH) potentially curable by pulmonary endarterectomy (PEA). Unfortunately, several patients have either an unacceptable risk-benefit ratio for undergoing the surgical intervention or develop persistent PH after PEA. Novel medical and endovascular therapies can be considered for them...
April 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29511676/effect-of-riociguat-and-sildenafil-on-right-heart-remodeling-and-function-in-pressure-overload-induced-model-of-pulmonary-arterial-banding
#10
Nabham Rai, Swathi Veeroju, Yves Schymura, Wiebke Janssen, Astrid Wietelmann, Baktybek Kojonazarov, Norbert Weissmann, Johannes-Peter Stasch, Hossein Ardeschir Ghofrani, Werner Seeger, Ralph Theo Schermuly, Tatyana Novoyatleva
Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by remodeling of the pulmonary vasculature and a rise in right ventricular (RV) afterload. The increased RV afterload leads to right ventricular failure (RVF) which is the reason for the high morbidity and mortality in PAH patients. The objective was to evaluate the therapeutic efficacy and antiremodeling potential of the phosphodiesterase type 5 (PDE5) inhibitor sildenafil and the soluble guanylate cyclase stimulator riociguat in a model of pressure overload RV hypertrophy induced by pulmonary artery banding (PAB)...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29470642/real-world-switching-to-riociguat-management-and-practicalities-in-patients-with-pah-and-cteph
#11
Henning Gall, Jean-Luc Vachiéry, Nobuhiro Tanabe, Michael Halank, Mauricio Orozco-Levi, Lisa Mielniczuk, MiKyung Chang, Kai Vogtländer, Ekkehard Grünig
PURPOSE: A proportion of patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) do not achieve treatment goals or experience side effects on their current therapy. In such cases, switching patients to a new drug while discontinuing the first may be a viable and appropriate treatment option. CAPTURE was designed to investigate how physicians manage the switching of patients to riociguat in real-world clinical practice. Observations from the study were used to assess whether recommendations in the riociguat prescribing information are reflected in clinical practice...
June 2018: Lung
https://www.readbyqxmd.com/read/29431644/induction-of-microrna-199-by-nitric-oxide-in-endothelial-cells-is-required-for-nitrovasodilator-resistance-via-targeting-of-prostaglandin-i2-synthase
#12
Yong-Ping Bai, Jia-Xiong Zhang, Quan Sun, Ji-Peng Zhou, Jing-Min Luo, Ling-Fang He, Xing-Chi Lin, Ling-Ping Zhu, Wan-Zhou Wu, Zhen-Yu Wang, Guo-Gang Zhang
Background -Nitrates are widely used to treat coronary artery disease, but their therapeutic value is compromised by nitrate tolerance, owing to the dysfunction of prostaglandin I2 synthase (PTGIS). Micro RNAs (miRNAs) repress target gene expression and are recognized as important epigenetic regulators of endothelial function. The aim of this study was to determine whether nitrates induce nitrovasodilator resistance via microRNA-dependent repression of PTGIS gene expression. Methods -Nitrovasodilator resistance was induced by nitroglycerin (GTN; 100 mg/kg/day, 3 days) infusion in Apoe -/- mice...
February 5, 2018: Circulation
https://www.readbyqxmd.com/read/29421995/new-drugs-therapeutic-strategies-and-future-direction-for-the-treatment-of-pulmonary-arterial-hypertension
#13
Valentina Mercurio, Anna Bianco, Giacomo Campi, Alessandra Cuomo, Nermin Diab, Angela Mancini, Paolo Parrella, Mario Petretta, Paul Hassoun, Domenico Bonaduce
Despite recent advances in pulmonary arterial hypertension (PAH) treatment, this condition is still characterized by an extremely poor prognosis. In this review, we discuss the use of newly-approved drugs for PAH treatment with already known mechanisms of action (macitentan), innovative targets (riociguat and selexipag), and novel therapeutic approaches with initial up-front combination therapy. Secondly, we describe new potential signalling pathways and investigational drugs with promising role in the treatment of PAH...
January 31, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29364918/riociguat-versus-sildenafil-on-hypoxic-pulmonary-vasoconstriction-and-ventilation-perfusion-matching
#14
COMPARATIVE STUDY
Virginia Chamorro, Daniel Morales-Cano, Javier Milara, Bianca Barreira, Laura Moreno, María Callejo, Gema Mondejar-Parreño, Sergio Esquivel-Ruiz, Julio Cortijo, Ángel Cogolludo, Joan A Barberá, Francisco Perez-Vizcaino
INTRODUCTION: Current treatment with vasodilators for pulmonary hypertension associated with respiratory diseases is limited by their inhibitory effect on hypoxic pulmonary vasoconstriction (HPV) and uncoupling effects on ventilation-perfusion (V'/Q'). Hypoxia is also a well-known modulator of the nitric oxide (NO) pathway, and may therefore differentially affect the responses to phosphodiesterase 5 (PDE5) inhibitors and soluble guanylyl cyclase (sGC) stimulators. So far, the effects of the sGC stimulator riociguat on HPV have been poorly characterized...
2018: PloS One
https://www.readbyqxmd.com/read/29344382/advanced-therapies-for-the-management-of-adults-with-pulmonary-arterial-hypertension-due-to-congenital-heart-disease-a-systematic-review
#15
Daniel L Varela, Mohamed Teleb, Wael El-Mallah
Pulmonary arterial hypertension (PAH) secondary to congenital heart disease (CHD) is the third most common cause of PAH, and it is becoming increasingly common as improvements in the management of CHD have led to increased life expectancy for these patients. The medical management of PAH due to CHD (PAH-CHD) is largely the same as what has been used for the treatment of idiopathic PAH, though the body of literature supporting this management decision is very small. There are currently few studies available which specifically focus on the treatment of PAH-CHD...
2018: Open Heart
https://www.readbyqxmd.com/read/29319041/successful-pulmonary-thromboendarterectomy-in-a-patient-with-sickle-cell-disease-and-associated-resolution-of-a-leg-ulcer
#16
Abhinav Agrawal, Rakesh Shah, Matthew D Bacchetta, Arunabh Talwar
Pulmonary hypertension (PH) is a relatively frequent and severe complication of sickle cell disease (SCD). PH associated with SCD is classified as Group 5 PH. The exact pathogenesis of PH in SCD in not known. There are also very limited treatment options available at this time for such patients with Group 5 PH. Patients with SCD are predisposed to a hypercoagulable state and thus can also suffer from chronic thromboembolism. These patients can have associated chronic thromboembolic pulmonary hypertension (CTEPH), thus being classified as Group 4 PH...
January 2018: Lung India: Official Organ of Indian Chest Society
https://www.readbyqxmd.com/read/29282032/riociguat-in-patients-with-chronic-thromboembolic-pulmonary-hypertension-results-from-an-early-access-study
#17
Vallerie V McLaughlin, Pavel Jansa, Jens E Nielsen-Kudsk, Michael Halank, Gérald Simonneau, Ekkehard Grünig, Silvia Ulrich, Stephan Rosenkranz, Miguel A Gómez Sánchez, Tomás Pulido, Joanna Pepke-Zaba, Joan Albert Barberá, Marius M Hoeper, Jean-Luc Vachiéry, Irene Lang, Francine Carvalho, Christian Meier, Katharina Mueller, Sylvia Nikkho, Andrea M D'Armini
BACKGROUND: Following positive results from the Phase III CHEST-1 study in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), the Phase IIIb CTEPH early access study (EAS) was designed to assess the safety and tolerability of riociguat in real-world clinical practice, as well as to provide patients with early access to riociguat before launch. Riociguat is approved for the treatment of inoperable and persistent/recurrent CTEPH. METHODS: We performed an open-label, uncontrolled, single-arm, early access study in which 300 adult patients with inoperable or persistent/recurrent CTEPH received riociguat adjusted from 1 mg three times daily (tid) to a maximum of 2...
December 28, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29275134/comparative-safety-of-drugs-targeting-the-nitric-oxide-pathway-in-pulmonary-hypertension-a-mixed-approach-combining-a-meta-analysis-of-clinical-trials-and-a-disproportionality-analysis-from-the-world-health-organization-pharmacovigilance-database
#18
Charles Khouri, Marion Lepelley, Matthieu Roustit, François Montastruc, Marc Humbert, Jean-Luc Cracowski
BACKGROUND: Recent guidelines recommend riociguat, a soluble guanylate cyclase (sGC) stimulator, and the type 5 phosphodiesterase inhibitor (PDE5i) tadalafil or sildenafil as treatments for pulmonary arterial hypertension. We compared the safety profiles of sildenafil, tadalafil, and riociguat in pulmonary hypertension. METHODS: We combined two approaches. First, we performed a meta-analysis of safety data extracted from randomized controlled trials. Second, we conducted a disproportionality analysis of data from VigiBase, the World Health Organization's global database of individual case safety reports, to compare the safety profiles with real-life data...
December 21, 2017: Chest
https://www.readbyqxmd.com/read/29251547/riociguat-a-soluble-guanylate-cyclase-stimulator-ameliorates-right-ventricular-contraction-in-pulmonary-arterial-hypertension
#19
Mitsushige Murata, Takashi Kawakami, Masaharu Kataoka, Takashi Kohno, Yuji Itabashi, Keiichi Fukuda
Riociguat is a soluble guanylate cyclase stimulator used for pulmonary hypertension (PH) treatment. We evaluated right ventricular (RV) contractile function in 27 PH patients receiving riociguat. A comparison of pre- and post-administration echocardiographic studies demonstrated significantly improved RV strain after riociguat treatment, even after adjusting for RV afterload.
January 2018: Pulmonary Circulation
https://www.readbyqxmd.com/read/29223470/reveal-risk-scores-applied-to-riociguat-treated-patients-in-patent-2-impact-of-changes-in-risk-score-on-survival
#20
Raymond L Benza, Harrison W Farber, Adaani Frost, Hossein-Ardeschir Ghofrani, Miguel A Gómez-Sánchez, David Langleben, Stephan Rosenkranz, Dennis Busse, Christian Meier, Sylvia Nikkho, Marius M Hoeper
BACKGROUND: The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) risk score (RRS) calculator was developed using data derived from the REVEAL registry, and predicts survival in patients with pulmonary arterial hypertension (PAH) based on multiple patient characteristics. Herein we applied the RRS to a pivotal PAH trial database, the 12-week PATENT-1 and open-label PATENT-2 extension studies of riociguat. We examined the effect of riociguat vs placebo on RRS in PATENT-1, and investigated the prognostic implications of change in RRS during PATENT-1 on long-term outcomes in PATENT-2...
November 11, 2017: Journal of Heart and Lung Transplantation
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