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https://www.readbyqxmd.com/read/27825893/evaluating-the-efficacy-safety-and-tolerability-of-serelaxin-when-added-to-standard-therapy-in-asian-patients-with-acute-heart-failure-the-design-and-rationale-of-relax-ahf-asia-trial
#1
Naoki Sato, Carolyn S P Lam, John R Teerlink, Barry H Greenberg, Hiroyuki Tsutsui, Byung-Hee Oh, Jian Zhang, Martin Lefkowitz, Tsushung A Hua, Thomas Holbro, Miriam Marshood, Xing Li Wang, Junbo Ge
BACKGROUND: Acute heart failure (AHF), a common and growing health-concern worldwide, is associated with high risk of post-discharge rehospitalization and mortality. Existing evidence indicates potential therapeutic benefits of serelaxin in Caucasian AHF patients, while corresponding data in Asians remain scarce. RELAX-AHF-ASIA, a multinational, randomized, double-blind, placebo-controlled, phase-III trial, will evaluate the effects of serelaxin on symptom relief and clinical outcomes in Asian AHF patients, using novel assessments...
November 4, 2016: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/27727514/serelaxin-in-acute-heart-failure-most-recent-update-on-clinical-and-preclinical-evidence
#2
Raktim Kumar Ghosh, Kinjal Banerjee, Ramyashree Tummala, Somedeb Ball, Keyvan Ravakhah, Anjan Gupta
Heart failure continues to be a widely prevalent disease across the world, affecting millions of Americans annually. Acute heart failure (AHF) has a substantial effect on rising health care costs and one of the major causes of morbidity and mortality. The search for new drugs for symptom relief and to improve long term outcomes in heart failure has led to development of serelaxin, a recombinant human relaxin-2 hormone. Relaxin was discovered in pregnancy but eventually found to have a number of other physiological actions, not only in pregnancy, but also in non-pregnant women and men...
October 11, 2016: Cardiovascular Therapeutics
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/27039129/use-of-high-sensitivity-troponin-t-to-identify%C3%A2-patients-with-acute-heart-failure-at%C3%A2-lower%C3%A2-risk-for-adverse-outcomes-an-exploratory-analysis-from-the-relax-ahf-trial
#4
Peter S Pang, John R Teerlink, Adriaan A Voors, Piotr Ponikowski, Barry H Greenberg, Gerasimos Filippatos, G Michael Felker, Beth A Davison, Gad Cotter, Joshua Kriger, Margaret F Prescott, Tsushung A Hua, Thomas Severin, Marco Metra
OBJECTIVES: The aim of this study was to determine if a baseline high-sensitivity troponin T (hsTnT) value ≤99th percentile upper reference limit (0.014 μg/l ["low hsTnT"]) identifies patients at low risk for adverse outcomes. BACKGROUND: Approximately 85% of patients who present to emergency departments with acute heart failure are admitted. Identification of patients at low risk might decrease unnecessary admissions. METHODS: A post-hoc analysis was conducted from the RELAX-AHF (Serelaxin, Recombinant Human Relaxin-2, for Treatment of Acute Heart Failure) trial, which randomized patients within 16 h of presentation who had systolic blood pressure >125 mm Hg, mild to moderate renal impairment, and N-terminal pro-brain natriuretic peptide ≥1,600 ng/l to serelaxin versus placebo...
July 2016: JACC. Heart Failure
https://www.readbyqxmd.com/read/27017514/effects-of-serelaxin-in-acute-heart-failure-patients-with-renal-impairment-results-from-relax-ahf
#5
Licette C Y Liu, Adriaan A Voors, John R Teerlink, Gad Cotter, Beth A Davison, G Michael Felker, Gerasimos Filippatos, Yakuan Chen, Barry H Greenberg, Piotr Ponikowski, Peter S Pang, Margaret F Prescott, Tsushung A Hua, Thomas M Severin, Marco Metra
BACKGROUND: Serelaxin showed beneficial effects on clinical outcome and trajectories of renal markers in patients with acute heart failure. We aimed to study the interaction between renal function and the treatment effect of serelaxin. METHODS: In the current post hoc analysis of the RELAX-AHF trial, we included all patients with available estimated glomerular filtration rate (eGFR) at baseline (n = 1132). Renal impairment was defined as an eGFR <60 ml/min/1...
September 2016: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/26719808/what-can-we-learn-from-relax-ahf-compared-to-previous-ahf-trials-and-what-does-the-future-hold
#6
REVIEW
Jane A Cannon, Andrew R McKean, Pardeep S Jhund, John J V McMurray
Each year in the USA there are over 1 million hospital admissions directly related to heart failure (HF). With similar rates across Europe, this places a huge economic burden on healthcare systems globally. Hospitalisation for HF is associated with poor clinical outcomes with 25% of patients being readmitted with signs and symptoms of HF within 1 month of discharge and 10-20% dying in the 6 months after discharge. Although hospital admission could be a sign of disease progression, it is also possible that some of the treatments given acutely for example, inotropic therapy, may result in neurohormonal, haemodynamic and other effects accelerating end-organ damage and contributing to these poor outcomes after discharge...
2015: Open Heart
https://www.readbyqxmd.com/read/26660642/time-dependent-activation-of-prostacyclin-and-nitric-oxide-pathways-during-continuous-i-v-infusion-of-serelaxin-recombinant-human-h2-relaxin
#7
C H Leo, M Jelinic, H H Ng, M Tare, L J Parry
BACKGROUND AND PURPOSE: In the RELAX-AHF trial, a 48 h i.v. serelaxin infusion reduced systemic vascular resistance in patients with acute heart failure. Consistent with preclinical studies, serelaxin augments endothelial vasodilator function in rat mesenteric arteries. Little is known about the contribution of endothelium-derived relaxing factors after a longer duration of continuous serelaxin treatment. Here we have assessed vascular reactivity and mechanistic pathways in mesenteric arteries and veins and the aorta after 48 or 72 h continuous i...
March 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/26603680/serelaxin-and-acute-heart-failure
#8
REVIEW
Jeremy Tietjens, John R Teerlink
Attempts at developing novel therapeutic agents for acute heart failure (AHF) over the past two decades have been marked by disappointment. Relaxin is a human peptide hormone believed to mediate many adaptive haemodynamic changes that occur during pregnancy. Because these effects may be useful for treating AHF, a recombinant version of human relaxin-2, serelaxin, has been developed as a novel therapeutic agent. Studies have confirmed serelaxin's haemodynamic effects of decreasing pulmonary and systemic resistance and increasing renal blood flow...
January 2016: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/26589290/relaxin-the-heart-a-novel-therapeutic-modality
#9
Juan M Valle Raleigh, Stefano Toldo, Anindita Das, Antonio Abbate, Fadi N Salloum
The peptide hormone relaxin has traditionally been linked to the maternal adaptation of the cardiovascular system during the first trimester of pregnancy. By promoting nitric oxide formation through different molecular signaling events, relaxin has been proposed as a pleiotropic and cardioprotective hormone in the setting of many cardiovascular diseases. In fact, preclinical studies were able to demonstrate that relaxin promotes vasodilatation and angiogenesis, ameliorates ischemia/reperfusion injury, and regulates extracellular matrix turnover and remodeling...
July 2016: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/26493539/enhanced-serelaxin-signalling-in-co-cultures-of-human-primary-endothelial-and-smooth-muscle-cells
#10
M Sarwar, C S Samuel, R A Bathgate, D R Stewart, R J Summers
BACKGROUND AND PURPOSE: In the phase III clinical trial, RELAX-AHF, serelaxin caused rapid and long-lasting haemodynamic changes. However, the cellular mechanisms involved are unclear in humans. EXPERIMENTAL APPROACH: This study examined the effects of serelaxin in co-cultures of human primary endothelial cells (ECs) and smooth muscle cells (SMCs) on cAMP and cGMP signalling. KEY RESULTS: Stimulation of HUVECs or human coronary artery endothelial cells (HCAECs) with serelaxin, concentration-dependently increased cGMP accumulation in co-cultured SMCs to a greater extent than in monocultures of either cell type...
February 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/26333655/serial-high-sensitivity-cardiac-troponin-t-measurement-in-acute-heart-failure-insights-from-the-relax-ahf-study
#11
RANDOMIZED CONTROLLED TRIAL
G Michael Felker, Robert J Mentz, John R Teerlink, Adriaan A Voors, Peter S Pang, Piotr Ponikowski, Barry H Greenberg, Gerasimos Filippatos, Beth A Davison, Gad Cotter, Margaret F Prescott, Tsushung A Hua, Sara Lopez-Pintado, Thomas Severin, Marco Metra
AIMS: Troponin elevation is common in acute heart failure (AHF) and may be useful for prognostication; however, available data are mixed and many previous studies used older, less sensitive assays. We examined the association between serial measurements of high-sensitivity cardiac troponin T (hs-cTnT) and outcomes in RELAX-AHF. METHODS AND RESULTS: Hs-cTnT was measured at baseline and days 2, 5, and 14. We assessed the relationship between baseline, peak and peak change hs-cTnT with dyspnoea relief by visual analogue scale, cardiovascular death, or HF/renal hospitalization to 60 days and cardiovascular mortality to 180 days...
December 2015: European Journal of Heart Failure
https://www.readbyqxmd.com/read/26333529/growth-differentiation-factor-15-gdf-15-in-patients-admitted-for-acute-heart-failure-results-from-the-relax-ahf-study
#12
RANDOMIZED CONTROLLED TRIAL
Gad Cotter, Adriaan A Voors, Margaret F Prescott, G Michael Felker, Gerasimos Filippatos, Barry H Greenberg, Peter S Pang, Piotr Ponikowski, Olga Milo, Tsushung A Hua, Min Qian, Thomas M Severin, John R Teerlink, Marco Metra, Beth A Davison
BACKGROUND: Growth differentiation factor 15 (GDF-15) was found to be upregulated in patients with chronic heart failure (HF) and associated with disease severity, however, data on patients with acute heart failure (AHF) is lacking. METHODS AND RESULTS: Levels of GDF-15 were measured at pre-specified time-points (baseline and at days 2, 5, 14, and 60) in patients enrolled in the placebo-controlled RELAXin in Acute Heart Failure (RELAX-AHF) study, which examined the effect of serelaxin in 1161 patients with AHF, systolic blood pressure >125 mmHg, and mild to moderate renal impairment...
November 2015: European Journal of Heart Failure
https://www.readbyqxmd.com/read/26294074/serelaxin-a-novel-treatment-for-acute-heart-failure
#13
REVIEW
Anna Isotta Castrini, Valentina Carubelli, Valentina Lazzarini, Ivano Bonadei, Carlo Lombardi, Marco Metra
Acute heart failure (AHF) represents a major healthcare burden with a high risk of in-hospital and post-discharge mortality, which remained almost unchanged in the last few decades, underscoring the need of new treatments. Relaxin is a naturally occurring human peptide initially identified as a reproductive hormone and has been shown to play a key role in the maternal hemodynamic and renal adjustments that accommodate pregnancy. Recently, the new molecule serelaxin, a recombinant form of the naturally occurring hormone relaxin has been studied in patients hospitalized for AHF...
2015: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/25959752/-the-relax-ahf-study
#14
Andrea Mortara
No abstract text is available yet for this article.
April 2015: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/25951761/worsening-heart-failure-following-admission-for-acute-heart-failure-a-pooled-analysis-of-the-protect-and-relax-ahf-studies
#15
RANDOMIZED CONTROLLED TRIAL
Beth A Davison, Marco Metra, Gad Cotter, Barry M Massie, John G F Cleland, Howard C Dittrich, Christopher Edwards, Gerasimos Filippatos, Michael M Givertz, Barry Greenberg, Piotr Ponikowski, Adriaan A Voors, Christopher M O'Connor, John R Teerlink
OBJECTIVES: These studies conducted analyses to examine patient characteristics and outcomes associated with worsening heart failure (WHF). BACKGROUND: WHF during an admission for acute heart failure (AHF) represents treatment failure and is a potential therapeutic target for clinical trials of AHF. METHODS: Individual patient data from the PROTECT (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function) and RELAX-AHF (Relaxin in Acute Heart Failure) phase II and III studies were pooled for analysis...
May 2015: JACC. Heart Failure
https://www.readbyqxmd.com/read/25903109/how-does-a-clinical-trial-fit-into-the-real-world-the-relax-ahf-study-population-into-the-eahfe-registry
#16
RANDOMIZED CONTROLLED TRIAL
Òscar Miró, Víctor Gil, Christian Müller, Alexander Mebazaa, Héctor Bueno, Francisco Javier Martín-Sánchez, Pablo Herrero, Javier Jacob, Pere Llorens
OBJECTIVE: To test how accurate the recently published RELAX-AHF trial was in recruiting real-world patients with acute-decompensated heart failure (ADHF). METHODS AND RESULTS: We compared clinical and outcome data of patients receiving serelaxin in the RELAX-AHF trial (RELAX group, n = 581) with patients included in the EAHFE registry [5497 ADHF from 29 Spanish emergency departments (EDs)]. The EAHFE registry was split into two groups: EAHFE-non-RELAX (patients not fulfilling the RELAX-AHF inclusion criteria; n = 3205, 58...
October 2015: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/25301463/effect-of-serelaxin-on-mode-of-death-in-acute-heart-failure-results-from-the-relax-ahf-study
#17
RANDOMIZED CONTROLLED TRIAL
G Michael Felker, John R Teerlink, Javed Butler, Adrian F Hernandez, Alan B Miller, Gad Cotter, Beth A Davison, Gerasimos Filippatos, Barry H Greenberg, Piotr Ponikowski, Adriaan A Voors, Tsushung A Hua, Thomas M Severin, Elaine Unemori, Marco Metra
BACKGROUND: Little is known about mode of death after acute heart failure (AHF) hospitalization. In the RELAX-AHF (Efficacy and Safety of Relaxin for the Treatment of Acute Heart Failure) study, serelaxin, the recombinant form of human relaxin-2, reduced post-discharge mortality at 180 days in selected patients with AHF. OBJECTIVES: The goal of this study was to assess the effect of serelaxin on specific modes of death in patients with AHF. METHODS: The RELAX-AHF study randomized 1,161 patients with AHF to 48 h of therapy with intravenous serelaxin or placebo...
October 14, 2014: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/25297987/serelaxin-mediated-signal-transduction-in-human-vascular-cells-bell-shaped-concentration-response-curves-reflect-differential-coupling-to-g-proteins
#18
M Sarwar, C S Samuel, R A Bathgate, D R Stewart, R J Summers
BACKGROUND AND PURPOSE: In a recently conducted phase III clinical trial, RELAX-AHF, serelaxin infusion over 48 h improved short- and long-term clinical outcomes in patients with acute heart failure. In this study we used human primary cells from the umbilical vasculature to better understand the signalling mechanisms activated by serelaxin. EXPERIMENTAL APPROACH: We examined the acute effects of serelaxin on signal transduction mechanisms in primary human umbilical vascular cells and its chronic actions on markers of cardiovascular function and disease...
February 2015: British Journal of Pharmacology
https://www.readbyqxmd.com/read/25287144/diuretic-response-in-patients-with-acute-decompensated-heart-failure-characteristics-and-clinical-outcome-an-analysis-from-relax-ahf
#19
RANDOMIZED CONTROLLED TRIAL
Adriaan A Voors, Beth A Davison, John R Teerlink, G Michael Felker, Gad Cotter, Gerasimos Filippatos, Barry H Greenberg, Peter S Pang, Bruce Levin, Tsushung A Hua, Thomas Severin, Piotr Ponikowski, Marco Metra
AIMS: We studied the characteristics and clinical outcome related to diuretic response and the effects of serelaxin in patients hospitalized for acute heart failure (AHF). METHODS AND RESULTS: RELAX-AHF was a double-blind, placebo-controlled trial, enrolling 1161 patients admitted to hospital for AHF who were randomized to 48 h i.v infusions of placebo or serelaxin (30 µg/kg per day) within 16 h from presentation. Diuretic response was defined as Δ weight kg/[(total i...
November 2014: European Journal of Heart Failure
https://www.readbyqxmd.com/read/24934696/recombinant-human-relaxin-2-how-can-a-pregnancy-hormone-save-lives-in-acute-heart-failure
#20
REVIEW
Thomas Bernd Dschietzig
Acute heart failure (AHF) syndrome, characterized by pulmonary and/or venous congestion owing to increased cardiac filling pressures with or without diminished cardiac output, is still associated with high post-discharge mortality and hospitalization rates. Many novel and promising therapeutic approaches, among them endothelin-1, vasopressin and adenosine antagonists, calcium sensitization, and recombinant B-type natriuretic hormone, have failed in large studies. Likewise, the classic drugs, vasodilators, diuretics, and inotropes, have never been shown to lower mortality...
October 2014: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
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