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Riociguat

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https://www.readbyqxmd.com/read/29319041/successful-pulmonary-thromboendarterectomy-in-a-patient-with-sickle-cell-disease-and-associated-resolution-of-a-leg-ulcer
#1
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
#2
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-who-pharmacovigilance-database
#3
C Khouri, M Lepelley, M Roustit, F Montastruc, M Humbert, J L Cracowski
BACKGROUND: Recent guidelines recommend riociguat, a soluble guanylate cyclase (sGC) stimulator, as well as 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. Secondly, we conducted a disproportionality analysis of data from VigiBase, the WHO 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/express-riociguat-a-soluble-guanylate-cyclase-stimulator-ameliorates-right-ventricular-contraction-in-pulmonary-arterial-hypertension
#4
Mitsushige Murata, Takashi Kawakami, Masaharu Kataoka, Takashi Kohno, Yuji Itabashi, Keiichi Fukuda
No abstract text is available yet for this article.
January 1, 2017: 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
#5
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
https://www.readbyqxmd.com/read/29099661/first-in-child-use-of-the-oral-soluble-guanylate-cyclase-stimulator-riociguat-in-pulmonary-arterial-hypertension
#6
Till Spreemann, Harald Bertram, Christoph M Happel, Rainer Kozlik-Feldmann, Georg Hansmann
Riociguat has been approved for use in adults with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension. No clinical data on its therapeutic use in children with PAH are currently available. We report the case of a now four-year-old boy who initially presented at the age of 10 months with suprasystemic pulmonary hypertension (PH) and right ventricular (RV) failure, vomiting, peripheral cyanosis, and failure to thrive. Cardiac catheterization revealed severe PAH. At radiologic suspicion of interstitial lung disease, repeated CT scan and an open lung biopsy were performed but could not clarify the entity of PAH...
January 2018: Pulmonary Circulation
https://www.readbyqxmd.com/read/29051185/cgmp-elevating-compounds-and-ischemic-conditioning-provide-cardioprotection-against-ischemia-and-reperfusion-injury-via-cardiomyocyte-specific-bk-channels
#7
Sandra Frankenreiter, Piotr Bednarczyk, Angelina Kniess, Nadja Bork, Julia Straubinger, Piotr Koprowski, Antoni Wrzosek, Eva Mohr, Angela Logan, Michael P Murphy, Meinrad Gawaz, Thomas Krieg, Adam Szewczyk, Viacheslav O Nikolaev, Peter Ruth, Robert Lukowski
Background -The nitric oxide-sensitive guanylyl cyclase (NO-GC)/cyclic guanosine-3',5'-monophosphate (cGMP)/cGMP-dependent protein kinase type I (cGKI)-signaling pathway can afford protection against the ischemia and reperfusion (I/R) injury that occurs during myocardial infarction (MI). Reportedly, voltage and Ca(2+)-activated K(+) channels of the BK-type are stimulated by cGMP/cGKI and recent ex-vivo studies implicated that increased BK activity favors the survival of the myocardium at I/R. It remains unclear, however, whether the molecular events downstream of cGMP involve BK channels present in cardiomyocytes (CMs) or in other cardiac cell types...
October 19, 2017: Circulation
https://www.readbyqxmd.com/read/28980994/comparison-of-the-crystal-structures-and-thermochemistry-of-a-novel-soluble-guanylate-cyclase-stimulator-riociguat-and-its-solvates
#8
Xinbo Zhou, Xiurong Hu, Jianming Gu, Jianrong Zhu
Riociguat (Rio) is the first oral soluble guanylate cyclase stimulator to be approved for pulmonary arterial hypertension. In this study, form (II) of riociguat and three solvates with acetonitrile [form (III)], N,N-dimethylformamide [form (IV)] and ethyl acetate [form (V)] were crystallized. They were identified and characterized by differential scanning calorimetry, thermogravimetric analysis, X-ray powder diffraction, and their crystal structures were determined by single-crystal X-ray diffraction. No crystal structure has previously been reported for the known form (II) of riociguat...
October 1, 2017: Acta Crystallographica Section B, Structural Science, Crystal Engineering and Materials
https://www.readbyqxmd.com/read/28914189/a-hopeful-prospect-of-riociguat-as-a-soluble-guanylate-cyclase-stimulator-for-management-of-pressure-ulcers
#9
Soha Azadi, Hajar Ashrafi, Amir Azadi
Pressure ulcer remains as a common problem, especially developed in disabled patients and hence, subjected to continuous pressure for prolonged periods of time. Most of the studies investigating the preventive and therapeutic approaches have focused on wound cleansing, dressing and supportive strategies , as well as pharmacological therapy including zinc sulphate, vitamin A or phenytoin. Despite such efforts, pressure ulcer continues to impair the life quality and expectancy. Thus involving in the paradigm shift in biomedical studies, the recent ones focus on biological signaling pathways involving nitric oxide (NO)- soluble guanylatecyclase (sGC)- cyclic guanosine monophosphate (cGMP) contributing in vasodilation, reperfusion and oxygen delivery...
September 15, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28889107/respite-switching-to-riociguat-in-pulmonary-arterial-hypertension-patients-with-inadequate-response-to-phosphodiesterase-5-inhibitors
#10
Marius M Hoeper, Gérald Simonneau, Paul A Corris, Hossein-Ardeschir Ghofrani, James R Klinger, David Langleben, Robert Naeije, Pavel Jansa, Stephan Rosenkranz, Laura Scelsi, Ekkehard Grünig, Carmine Dario Vizza, MiKyung Chang, Pablo Colorado, Christian Meier, Dennis Busse, Raymond L Benza
A proportion of pulmonary arterial hypertension (PAH) patients do not reach treatment goals with phosphodiesterase-5 inhibitors (PDE5i). RESPITE investigated the safety, feasibility and benefit of switching from PDE5i to riociguat in these patients.RESPITE was a 24-week, open-label, multicentre, uncontrolled study. Patients in World Health Organization (WHO) functional class (FC) III, with 6-min walking distance (6MWD) 165-440 m, cardiac index <3.0 L·min-1·m-2 and pulmonary vascular resistance >400 dyn·s·cm-5 underwent a 1-3 day PDE5i treatment-free period before receiving riociguat adjusted up to 2...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28732819/individual-dose-adjustment-of-riociguat-in-patients-with-pulmonary-arterial-hypertension-and-chronic-thromboembolic-pulmonary-hypertension
#11
REVIEW
Nicholas S Hill, Franck F Rahaghi, Namita Sood, Reiner Frey, Hossein-Ardeschir Ghofrani
Riociguat is a soluble guanylate cyclase stimulator that has been approved for the treatment of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension following pulmonary endarterectomy. Riociguat is administered using an 8-week individual dose-adjustment scheme whereby a patient initially receives riociguat 1.0 mg three times daily (tid), and the dose is then increased every 2 weeks in the absence of hypotension, indicated by systolic blood pressure measurements and symptoms, up to a maximum dose of 2...
August 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28715904/considerations-for-optimal-management-of-patients-with-pulmonary-arterial-hypertension-a-multi-stakeholder-roundtable-discussion
#12
Sean M Studer, Martha Kingman, Luis Calo, H Eric Cannon, Jeffrey D Dunn, Thomas James, Sonya J Lewis, Robert J Gilkin, Janis A Pruett
A roundtable panel of national and regional managed care decision makers and providers met to discuss pulmonary arterial hypertension (PAH) and strategies for management. As a rare, complex disease with high economic costs and potentially devastating outcomes, PAH necessitates that managed care providers balance optimal care with efficient use of healthcare resources. PAH specialists are recognized by health plans as knowledgeable experts and integral partners in managing patients and resources. The diagnosis of PAH must be confirmed by a right heart catheterization...
May 2017: American Journal of Managed Care
https://www.readbyqxmd.com/read/28705306/riociguat-for-patients-with-chronic-thromboembolic-pulmonary-hypertension-usefulness-of-transitioning-from-phosphodiesterase-type-5-inhibitor
#13
Keiko Yamamoto, Nobuhiro Tanabe, Rika Suda, Akane Sasaki, Akane Matsumura, Ryogo Ema, Hajime Kasai, Fumiaki Kato, Ayumi Sekine, Rintaro Nishimura, Takayuki Jujo, Toshihiko Sugiura, Ayako Shigeta, Seiichiro Sakao, Koichiro Tatsumi
BACKGROUND: Riociguat, the first approved drug for patients with chronic thromboembolic pulmonary hypertension (CTEPH), is a soluble guanylate cyclase (sGC) Stimulator. It directly stimulates sGC independently of nitric oxide (NO) and increases sGC sensitivity for NO. The safety and efficacy of transitioning from a phosphodiesterase 5 inhibitor (PDE5i) to riociguat is unknown. METHODS AND RESULTS: Twenty-three patients were prospectively enrolled: 8 symptomatic patients with inadequate clinical responses to PDE5i were changed to riociguat (transitioned group); 15 started riociguat anew (new or add-on group)...
July 2017: Respiratory Investigation
https://www.readbyqxmd.com/read/28671485/replacing-a-phosphodiesterase-5-inhibitor-with-riociguat-in-patients-with-connective-tissue-disease-associated-pulmonary-arterial-hypertension-a-case-series
#14
Amresh Raina, Raymond L Benza, Harrison W Farber
Patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-PAH-CTD) such as systemic sclerosis (SSc) have a poorer response to treatment and increased mortality compared with patients with idiopathic PAH. Current treatment options for PAH-CTD include prostanoids, phosphodiesterase type-5 inhibitors (PDE-5i), endothelin receptor antagonists, and the soluble guanylate cyclase stimulator riociguat. In this case series, we describe three patients with PAH-CTD related to limited scleroderma who were switched from a PDE-5i to riociguat due to insufficient clinical response...
July 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28652963/switching-from-sildenafil-to-riociguat-for-the-treatment-of-pah-and-inoperable-cteph-real-life-experiences
#15
Asger Andersen, Kasper Korsholm, Søren Mellemkjær, Jens Erik Nielsen-Kudsk
Riociguat is a novel soluble guanylate cyclase stimulator that is approved for the treatment of patients with pulmonary arterial hypertension (PAH) and patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA). As riociguat is a relatively new drug, experience of its use in clinical practice is limited, especially in patients who would not have met the inclusion criteria for the pivotal Phase III clinical trials, PATENT-1 and CHEST-1...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28610669/riociguat-for-pulmonary-arterial-hypertension-and-chronic-thromboembolic-pulmonary-hypertension-results-from-a-phase-ii-long-term-extension-study
#16
Michael Halank, Marius M Hoeper, Hossein-Ardeschir Ghofrani, F Joachim Meyer, Gerd Stähler, Jürgen Behr, Ralf Ewert, Monique Fletcher, Pablo Colorado, Sylvia Nikkho, Friedrich Grimminger
BACKGROUND: Riociguat was well tolerated and improved exercise and functional capacity in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH) in a 12-week Phase II trial. We present final data from the long-term extension phase of this study. METHODS: During this multicenter, open-label, uncontrolled long-term extension study, riociguat dose could be changed at the physician's discretion (range 0...
July 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28597779/phosphodiesterase-type-5-inhibitor-to-riociguat-transition-is-associated-with-hemodynamic-and-symptomatic-improvement-in-pulmonary-hypertension
#17
Ryan Davey, Raymond L Benza, Srinivas Murali, Amresh Raina
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...
April 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28557445/discovery-of-the-soluble-guanylate-cyclase-stimulator-vericiguat-bay-1021189-for-the-treatment-of-chronic-heart-failure
#18
Markus Follmann, Jens Ackerstaff, Gorden Redlich, Frank Wunder, Dieter Lang, Armin Kern, Peter Fey, Nils Griebenow, Walter Kroh, Eva-Maria Becker-Pelster, Axel Kretschmer, Volker Geiss, Volkhart Li, Alexander Straub, Joachim Mittendorf, Rolf Jautelat, Hartmut Schirok, Karl-Heinz Schlemmer, Klemens Lustig, Michael Gerisch, Andreas Knorr, Hanna Tinel, Thomas Mondritzki, Hubert Trübel, Peter Sandner, Johannes-Peter Stasch
The first-in-class soluble guanylate cyclase (sGC) stimulator riociguat was recently introduced as a novel treatment option for pulmonary hypertension. Despite its outstanding pharmacological profile, application of riociguat in other cardiovascular indications is limited by its short half-life, necessitating a three times daily dosing regimen. In our efforts to further optimize the compound class, we have uncovered interesting structure-activity relationships and were able to decrease oxidative metabolism significantly...
June 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28513869/transition-of-intravenous-treprostinil-to-oral-therapy-in-a-patient-with-functional-class-iv-chronic-thromboembolic-pulmonary-hypertension
#19
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...
August 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28458514/riociguat-a-soluble-guanylate-cyclase-stimulator-for-the-treatment-of-pulmonary-hypertension
#20
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
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