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Macitentan

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https://www.readbyqxmd.com/read/28329315/seraphin-haemodynamic-sub-study-the-effect-of-the-dual-endothelin-receptor-antagonist-macitentan-on-haemodynamic-parameters-and-nt-probnp-levels-and-their-association-with-disease-progression-in-patients-with-pulmonary-arterial-hypertension
#1
Nazzareno Galiè, Pavel Jansa, Tomás Pulido, Richard N Channick, Marion Delcroix, Hossein-Ardeschir Ghofrani, Franck-Olivier Le Brun, Sanjay Mehta, Loïc Perchenet, Lewis J Rubin, B K S Sastry, Gérald Simonneau, Olivier Sitbon, Rogério Souza, Adam Torbicki
Aims: The effect of macitentan on haemodynamic parameters and NT-proBNP levels was evaluated in pulmonary arterial hypertension (PAH) patients in the SERAPHIN study. Association between these parameters and disease progression, assessed by the primary endpoint (time to first morbidity/mortality event), was explored. Methods and results: Of the 742 randomized patients, 187 with right heart catheterization at baseline and month 6 participated in a haemodynamic sub-study...
February 28, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28300593/functional-estimation-of-endothelin-1-receptor-antagonism-by-bosentan-macitentan-and-ambrisentan-in-human-pulmonary-and-radial-arteries-in-vitro
#2
James A Angus, Paul F Soeding, Richard J A Hughes, Christine E Wright
BACKGROUND: Endothelin receptor antagonists are approved for pulmonary arterial hypertension. Development of selective ETA-receptor antagonists over mixed or dual receptor antagonists has depended on a range of receptor binding assays, second messenger assays and functional blood vessel assays. This study compared the 3 clinically-approved endothelin receptor antagonists in assays of human isolated pulmonary and radial arteries in vitro. METHODS: Human isolated pulmonary (i...
March 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28283234/endothelin-inhibitors-lower-pulmonary-vascular-resistance-and-improve-functional-capacity-in-patients-with-fontan-circulation
#3
Gabriella Agnoletti, Simona Gala, Francesca Ferroni, Roberto Bordese, Lorenzo Appendini, Carlo Pace Napoleone, Laura Bergamasco
OBJECTIVES: To evaluate the effects of endothelin inhibitors (ERAs) on hemodynamic and functional parameters in patients post-Fontan procedure with high pulmonary vascular resistance (PVR). METHODS: Among our cohort of patients with Fontan circulation, 8 children, 8 adolescents, and 8 adults had PVR ≥2 WU*m(2). These patients were treated with ERAs (minors with bosentan, adults with macitentan) and reevaluated after 6 months. Pre- and posttreatment hemodynamic variables were assessed by cardiac catheterization...
February 10, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28257550/tolerability-of-switch-to-macitentan-from-bosentan-in-pulmonary-arterial-hypertension
#4
Zeenat Safdar, Aishwarya Thakur, Adaani Frost
OBJECTIVES: Pulmonary arterial hypertension (PAH) is a progressive disease that can be treated with several medications. Macitentan, an endothelin receptor antagonist (ERA), has received approval as a PAH therapy. We report our data regarding the tolerability in patients with PAH who were switched from bosentan to macitentan. METHODS: At the Baylor Pulmonary Hypertension Program, 24 patients with PAH who had been taking bosentan and were switched to macitentan were identified in this retrospective study...
March 2017: Southern Medical Journal
https://www.readbyqxmd.com/read/28237536/early-experience-of-macitentan-for-pulmonary-arterial-hypertension-in-adult-congenital-heart-disease
#5
S Herbert, W Gin-Sing, L Howard, R M R Tulloh
BACKGROUND: Endothelin receptor antagonists (ERA) have been recognised as effective therapy for pulmonary arterial hypertension in congenital heart disease (CHD-PH), and Eisenmenger syndrome (ES) since the Breathe 5 study. A new dual receptor antagonist - Macitentan - is currently undergoing trials to determine its efficacy in simple ES. To date there is little information on this therapy in CHD and we report our first experience, some with more complex diseases. METHODS: Data was collected prospectively from September 2014...
February 6, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28223322/eta-receptors-blockade-by-activating-etb-receptors-increases-vascular-permeability-and-induces-exaggerated-fluid-retention
#6
Magali Vercauteren, Frederic Trensz, Anne Pasquali, Christophe Cattaneo, Daniel S Strasser, Patrick Hess, Marc Iglarz, Martine Clozel
Endothelin receptor antagonists have been associated with fluid retention. It has been suggested that, of the two endothelin receptor subtypes, ETB receptors should not be blocked, because of their involvement in natriuresis and diuresis. Surprisingly, clinical data suggest that ETA-selective antagonists pose a greater risk of fluid overload than dual antagonists. The purpose of this study was to evaluate the contribution of each endothelin receptor to fluid retention and vascular permeability in rats. Sitaxentan and ambrisentan as ETA-selective antagonists, bosentan and macitentan as dual antagonists were used as representatives of each class, respectively...
February 21, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28134077/dual-endothelin-receptor-antagonists-contrast-the-effects-induced-by-endothelin-1-on-cultured-human-microvascular-endothelial-cells
#7
Stefano Soldano, Sabrina Paolino, Carmen Pizzorni, Amelia Chiara Trombetta, Paola Montagna, Renata Brizzolara, Claudio Corallo, Nicola Giordano, Alberto Sulli, Maurizio Cutolo
OBJECTIVES: To evaluate the ability of dual endothelin (ET) receptor antagonists (ETA/ETB -ETA/BRAs) to contrast the ET-1-induced effects on cultured human microvascular endothelial cells (HMVECs). METHODS: Some cultured HMVECs were untreated, or treated with ET-1 (100nM) or transforming growth factor β1 (TGFβ1, 10ng/mL) alone for 6 days, in order to induce the endothelial-to-mesenchymal transition (EndoMT). Other cultured HMVECs were pre-treated for 1hr with ETA/BRAs bosentan (10μM) or macitentan (1μM, 10μM) before the stimulation with ET-1 for 6 days...
January 27, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28120456/endothelin-1-mediates-natriuresis-but-not-polyuria-during-vitamin-d-induced-acute-hypercalcemia
#8
Natsuko Tokonami, Lydie Cheval, Isabelle Monnay, Guillaume Meurice, Johaness Loffing, Eric Feraille, Pascal Houillier
Acute hypercalcemia increases urinary sodium and water excretion; however, the underlying molecular mechanism remains unclear. As vitamin D-induced hypercalcemia increases the renal expression of endothelin (ET)-1, we hypothesized that ET-1 mediates the effects of hypercalcemia on renal sodium and water handling. Hypercalcemia was induced in 8 week-old, PTH-supplemented, male mice by oral administration of dihydrotachysterol (DHT) for 3 days. DHT-treated mice became hypercalcemic and displayed increased urinary water and sodium excretion compared to controls...
January 24, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28049880/pharmacological-and-clinical-profile-of-a-novel-dual-endothelin-receptor-antagonist-macitentan-opsumit-%C3%A2
#9
Shuya Takahashi, Ritsuko Horie, Yoshinari Yokoyama
No abstract text is available yet for this article.
2017: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/27994906/swift-and-complete-healing-of-digital-ulcers-after-macitentan-treatment
#10
Emilio Giner Serret
Digital ulcers are a burdensome and painful condition with sparse options of treatment. We report the case of a 78-year-old female patient with limited cutaneous systemic sclerosis that sequentially developed digital ulcers. After the appearance of digital ulcers in the soles of her feet she was successfully treated with bosentan. The report of two new digital ulcers in her hands 9 months later alongside with elevated transaminase levels led to a switch to macitentan treatment. A swift and complete healing of both digital ulcers was observed after 3 months, with the restoration of normal biochemical values...
2016: Case Reports in Rheumatology
https://www.readbyqxmd.com/read/27990270/recent-advances-in-the-management-of-pulmonary-arterial-hypertension
#11
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/27912207/clinical-adverse-effects-of-endothelin-receptor-antagonists-insights-from-the-meta-analysis-of-4894-patients-from-24-randomized-double-blind-placebo-controlled-clinical-trials
#12
Anhua Wei, Zhichun Gu, Juan Li, Xiaoyan Liu, Xiaofan Wu, Yi Han, Jun Pu
BACKGROUND: Evidence of the clinical safety of endothelin receptor antagonists (ERAs) is limited and derived mainly from individual trials; therefore, we conducted a meta-analysis. METHODS AND RESULTS: After systematic searches of the Medline, Embase, and Cochrane Library databases and the ClinicalTrials.gov website, randomized controlled trials with patients receiving ERAs (bosentan, macitentan, or ambrisentan) in at least 1 treatment group were included. All reported adverse events of ERAs were evaluated...
October 26, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27867974/is-macitentan-not-a-treatment-option-for-digital-ulcers-in-systemic-sclerosis
#13
EDITORIAL
Yoshihide Asano
No abstract text is available yet for this article.
October 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27846462/from-bosentan-to-macitentan-for-pulmonary-arterial-hypertension-and-adult-congenital-heart-disease-further-improvement
#14
Ilja M Blok, Annelieke C M J van Riel, Arie P J van Dijk, Barbara J M Mulder, Berto J Bouma
No abstract text is available yet for this article.
January 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27810862/dual-endothelin-a-endothelin-b-receptor-blockade-and-cardiac-remodeling-in-heart-failure-with-preserved-ejection-fraction
#15
Maria Valero-Munoz, Shanpeng Li, Richard M Wilson, Batbold Boldbaatar, Marc Iglarz, Flora Sam
BACKGROUND: Despite the increasing prevalence of heart failure with preserved ejection fraction (HFpEF) in humans, there remains no evidence-based therapies for HFpEF. Endothelin-1 (ET-1) antagonists are a possibility because elevated ET-1 levels are associated with adverse cardiovascular effects, such as arterial and pulmonary vasoconstriction, impaired left ventricular (LV) relaxation, and stimulation of LV hypertrophy. LV hypertrophy is a common phenotype in HFpEF, particularly when associated with hypertension...
November 2016: Circulation. Heart Failure
https://www.readbyqxmd.com/read/27716320/bosentan-and-macitentan-prevent-the-endothelial-to-mesenchymal-transition-endomt-in-systemic-sclerosis-in-vitro-study
#16
Claudio Corallo, Maurizio Cutolo, Bashar Kahaleh, Gianluca Pecetti, Antonio Montella, Chiara Chirico, Stefano Soldano, Ranuccio Nuti, Nicola Giordano
BACKGROUND: Systemic sclerosis (SSc) is characterized by early vascular abnormalities and subsequent fibroblast activation to myofibroblasts, leading to fibrosis. Recently, endothelial-to-mesenchymal transition (EndoMT), a complex biological process in which endothelial cells lose their specific markers and acquire a mesenchymal or myofibroblastic phenotype, has been reported in SSc. In the present study, we evaluated the ability of endothelin-1 (ET-1) dual receptor antagonists bosentan (BOS) and macitentan (MAC) to antagonize EndoMT in vitro...
October 6, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27688036/effects-of-an-endothelin-receptor-antagonist-macitentan-on-right-ventricular-substrate-utilization-and-function-in-a-sugen-5416-hypoxia-rat-model-of-severe-pulmonary-arterial-hypertension
#17
Katarzyna Drozd, Ali Ahmadi, Yupu Deng, Baohua Jiang, Julia Petryk, Stephanie Thorn, Duncan Stewart, Rob Beanlands, Robert A deKemp, Jean N DaSilva, Lisa M Mielniczuk
BACKGROUND: Altered myocardial energy metabolism has been linked to worsening of RV function in pulmonary arterial hypertension (PAH). The aim of this study was to evaluate RV glucose and fatty acid metabolism in vivo in a rat model of PAH using positron emission tomography (PET) and investigate the effects of Macitentan on RV substrate utilization. METHODS: PAH was induced in male Sprague-Dawley rats by a single subcutaneous injection of Sugen 5416 (20 mg/kg) followed by 3 weeks of hypoxia (10% oxygen)...
September 29, 2016: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
https://www.readbyqxmd.com/read/27671974/macitentan-improves-health-related-quality%C3%A2-of-life-for-patients-with-pulmonary-arterial-hypertension-results-from-the-randomized-controlled-seraphin-trial
#18
Sanjay Mehta, Bhagavatula Kutumba Srinivasa Sastry, Rogério Souza, Adam Torbicki, Hossein-Ardeschir Ghofrani, Richard N Channick, Marion Delcroix, Tomás Pulido, Gérald Simonneau, John Wlodarczyk, Lewis J Rubin, Pavel Jansa, Elke Hunsche, Nazzareno Galiè, Loïc Perchenet, Olivier Sitbon
BACKGROUND: Pulmonary arterial hypertension (PAH) leads to reduced health-related quality of life (HRQoL). The objectives of this analysis were to evaluate the effect of macitentan on HRQoL in patients with PAH in the Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome (SERAPHIN) study. The association between baseline HRQoL and long-term outcomes was also investigated. METHODS: Patients were randomized to placebo, macitentan 3 mg, or macitentan 10 mg once daily...
January 2017: Chest
https://www.readbyqxmd.com/read/27627939/update-on-pharmacotherapy-for-pulmonary-hypertension
#19
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/27580996/macitentan-a-review-in-pulmonary-arterial-hypertension
#20
REVIEW
Gillian M Keating
Macitentan (Opsumit(®)) is an orally active, potent, dual endothelin (ET) receptor antagonist that is indicated for the treatment of pulmonary arterial hypertension (PAH). In the pivotal SERAPHIN trial in patients aged ≥12 years with PAH, the risk of first PAH-related event or all-cause death (primary composite endpoint) was significantly reduced by 45 % with oral macitentan 10 mg once daily versus placebo. Macitentan significantly reduced the risk of the primary composite endpoint across various patient subgroups...
December 2016: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
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