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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/27545139/novel-therapies-for-heart-failure%C3%A3-where-do-they-stand
#2
Barry Greenberg
Despite advances in therapy, patients with heart failure (HF) continue to experience unacceptably high rates of hospitalization and death, as well as poor quality of life. As a consequence, there is an urgent need for new treatments that can improve the clinical course of the growing worldwide population of HF patients. Serelaxin and ularatide, both based on naturally occurring peptides, have potent vasodilatory as well as other effects on the heart and kidneys. For both agents, phase 3 studies that are designed to determine whether they improve outcomes in patients with acute HF have completed enrollment...
August 25, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27104862/potential-new-drug-treatments-for-congestive-heart-failure
#3
Hao A Tran, Felice Lin, Barry H Greenberg
INTRODUCTION: The prevalence of heart failure (HF) has increased globally in recent decades. Advances in our understanding of underlying pathophysiologic mechanisms have given rise to new therapies for treating the growing HF population. Nonetheless, morbidity and mortality associated with HF and its financial implications are daunting. Thus, novel therapies that can improve the natural history of HF patients are urgently needed. AREAS COVERED: This article reviews new investigational drugs being developed for the treatment of both acute decompensated heart failure (ADHF) and chronic heart failure with reduced ejection fraction (HFrEF)...
July 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/26850077/agents-with-vasodilator-properties-in-acute-heart-failure
#4
Abhishek Singh, Saïd Laribi, John R Teerlink, Alexandre Mebazaa
Millions of patients worldwide are admitted for acute heart failure (AHF) each year and physicians caring for these patients are confronted with the short-term challenges of reducing symptoms while preventing end organ dysfunction without causing additional harm, and the intermediate-term challenges of improving clinical outcomes such as hospital readmission and survival. There are limited data demonstrating the efficacy of any currently available therapies for AHF to meet these goals. After diuretics, vasodilators are the most common intravenous therapy for AHF, but neither nitrates, nitroprusside, nor nesiritide have robust evidence supporting their ability to provide meaningful effects on clinical outcomes, except perhaps early symptom improvement...
February 4, 2016: European Heart Journal
https://www.readbyqxmd.com/read/26547357/effect-of-vericiguat-a-soluble-guanylate-cyclase-stimulator-on-natriuretic-peptide-levels-in-patients-with-worsening-chronic-heart-failure-and-reduced-ejection-fraction-the-socrates-reduced-randomized-trial
#5
RANDOMIZED CONTROLLED TRIAL
Mihai Gheorghiade, Stephen J Greene, Javed Butler, Gerasimos Filippatos, Carolyn S P Lam, Aldo P Maggioni, Piotr Ponikowski, Sanjiv J Shah, Scott D Solomon, Elisabeth Kraigher-Krainer, Eliana T Samano, Katharina Müller, Lothar Roessig, Burkert Pieske
IMPORTANCE: Worsening chronic heart failure (HF) is a major public health problem. OBJECTIVE: To determine the optimal dose and tolerability of vericiguat, a soluble guanylate cyclase stimulator, in patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF). DESIGN, SETTING, AND PARTICIPANTS: Dose-finding phase 2 study that randomized 456 patients across Europe, North America, and Asia between November 2013 and January 2015, with follow-up ending June 2015...
December 1, 2015: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/25645316/renal-effects-of-soluble-guanylate-cyclase-stimulators-and-activators-a-review-of-the-preclinical-evidence
#6
REVIEW
Johannes-Peter Stasch, Jens Schlossmann, Berthold Hocher
Direct stimulation of soluble guanylate cyclase (sGC) is emerging as a potential new approach for the treatment of renal disorders. sGC catalyzes the formation of cyclic guanosine monophosphate (cGMP), deficiency of which is implicated in the pathogenesis of chronic kidney disease (CKD). Therefore, new classes of drugs - sGC stimulators and activators - are being investigated in preclinical models under conditions where nitric oxide is deficient. In preclinical models with different etiologies of CKD, the sGC stimulators BAY 41-2272, BAY 41-8543, BAY 60-4552, riociguat and vericiguat and the sGC activators cinaciguat, ataciguat, BI 703704 and GSK2181236A have shown consistently renoprotective effects...
April 2015: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/25056511/rationale-and-design-of-the-soluble-guanylate-cyclase-stimulator-in-heart-failure-studies-socrates
#7
RANDOMIZED CONTROLLED TRIAL
Burkert Pieske, Javed Butler, Gerasimos Filippatos, Carolyn Lam, Aldo Pietro Maggioni, Piotr Ponikowski, Sanjiv Shah, Scott Solomon, Elisabeth Kraigher-Krainer, Eliana Tibana Samano, Andrea Viviana Scalise, Katharina Müller, Lothar Roessig, Mihai Gheorghiade
AIMS: The clinical outcomes for patients with worsening chronic heart failure (WCHF) remain exceedingly poor despite contemporary evidence-based therapies, and effective therapies are urgently needed. Accumulating evidence supports augmentation of cyclic guanosine monophosphate (cGMP) signalling as a potential therapeutic strategy for HF with reduced or preserved ejection fraction (HFrEF and HFpEF, respectively). Direct soluble guanylate cyclase (sGC) stimulators target reduced cGMP generation due to insufficient sGC stimulation and represent a promising method for cGMP enhancement...
September 2014: European Journal of Heart Failure
https://www.readbyqxmd.com/read/24092345/soluble-guanylate-cyclase-stimulators-in-pulmonary-hypertension
#8
REVIEW
Johannes-Peter Stasch, Oleg V Evgenov
Soluble guanylate cyclase (sGC) is a key enzyme in the nitric oxide (NO) signalling pathway. On binding of NO to its prosthetic haem group, sGC catalyses the synthesis of the second messenger cyclic guanosine monophosphate (cGMP), which promotes vasodilation and inhibits smooth muscle proliferation, leukocyte recruitment, platelet aggregation and vascular remodelling through a number of downstream mechanisms. The central role of the NO-sGC-cGMP pathway in regulating pulmonary vascular tone is demonstrated by the dysregulation of NO production, sGC activity and cGMP degradation in pulmonary hypertension (PH)...
2013: Handbook of Experimental Pharmacology
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