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https://www.readbyqxmd.com/read/29623915/the-relaxin-peptide-family-potential-future-hope-for-neuroprotective-therapy-a-short-review
#1
REVIEW
Marius Nistor, Martin Schmidt, René Schiffner
Since its discovery in the 1920's the relaxin peptide hormone family has not only grown in number to now seven members (relaxin-1, relaxin-2, relaxin-3, insulin-like peptide (INSL) 3, INSL4, INSL5 and INSL6), but ever more effects, suchs as vasodilatory, angiogenic, anti-apoptopic, anti-fibriotic and anti-inflammatory, have been linked to them. While relaxin-2 has mainly been investigated in the context of cardiac protection, most comprehensively in the RELAX-AHF and RELAX AHF2 studies, a small number of studies have furthermore assessed the potential neuroprotective effects of especially relaxin-2 and other members of the relaxin family...
March 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29306479/site-enrollment-rate-outcomes-and-study-drug-effects-in-a-multicenter-trial-results-from-relax-ahf
#2
Marco Metra, Beth A Davison, Claudio Gimpelewicz, Valentina Carubelli, G Michael Felker, Gerasimos Filippatos, Barry H Greenberg, Tsushung A Hua, Zoe Liu, Peter S Pang, Piotr Ponikowski, Thomas M Severin, Adriaan A Voors, Yi Wang, Gad Cotter, John R Teerlink
BACKGROUND: Site selection is critical in acute heart failure trials. We assessed whether the enrollment rate per site affects patients' characteristics, outcomes and treatment response. METHODS AND RESULTS: A total of 1161 patients enrolled at 96 sites in the RELAX-AHF trial (serelaxin vs placebo) were included. Annualized enrollment rate was calculated as the total number of patients enrolled at each site divided by time that the site was open (patients per year)...
February 15, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/28939928/acute-heart-failure-an-unmet-medical-need
#3
REVIEW
A G Rigopoulos, C Bakogiannis, R de Vecchis, S Sakellaropoulos, M Ali, M Teren, M Matiakis, C Tschoepe, M Noutsias
Despite recent advances in the management of heart failure with reduced ejection fraction (HFrEF), the burden of acute heart failure (AHF) remains significant with a high morbidity and mortality that has not been improved by any treatment modality. A meta-analysis summarized the study results on the effects of tolvaptan on AHF, which failed to demonstrate an improvement in short-term and long-term mortality, length of hospital stay and reduced frequency of worsening heart failure (WHF). Similar trial results were also reported in other AHF studies, such as the ASCEND-HF and the RELAX-AHF-2 trials...
September 22, 2017: Herz
https://www.readbyqxmd.com/read/28836728/relax-ahf-blast-ahf-true-ahf-and-other-important-truths-in-acute-heart-failure-research
#4
EDITORIAL
Gad Cotter, Alain Cohen-Solal, Beth A Davison, Alexandre Mebazaa
No abstract text is available yet for this article.
November 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28760204/effects-of-serelaxin-on-the-outcome-of-patients-with-or-without-substantial-peripheral-edema-a-subgroup-analysis-from-the-relax-ahf-trial
#5
RANDOMIZED CONTROLLED TRIAL
Claudio Gimpelewicz, Marco Metra, John G F Cleland, Peter Szecsödy, Chuan-Chuan Chang Wun, Leandro Boer-Martins, Gad Cotter, Beth A Davison, Gary Michael Felker, Gerasimos Filippatos, Barry H Greenberg, Peter Pang, Piotr Ponikowski, Thomas Severin, Adrian A Voors, John R Teerlink
BACKGROUND: Acute heart failure (AHF) is a heterogeneous disorder, with most of the patients presenting with breathlessness along with varying degrees of peripheral edema. The presence of peripheral edema suggests that volume overload is the cause of decompensation leading to AHF, whereas breathlessness in the absence of edema may reflect a "vascular phenotype." This analysis investigated the characteristics, therapeutic response, and outcome of patients with AHF, with and without overt peripheral edema in the RELAX-AHF trial...
August 2017: American Heart Journal
https://www.readbyqxmd.com/read/28752374/erratum-to-serelaxin-in-acute-heart-failure-patients-with-and-without-atrial-fibrillation-a-secondary-analysis-of-the-relax-ahf-trial
#6
Gerasimos Filippatos, Dimitrios Farmakis, Marco Metra, Gad Cotter, Beth A Davison, G Michael Felker, Barry H Greenberg, Tsushung A Hua, Peter S Pang, Piotr Ponikowski, Min Qian, Thomas A Severin, Adriaan A Voors, John R Teerlink
No abstract text is available yet for this article.
November 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28583677/how-trialists-and-pharmaceutical-sponsors-have-failed-us-by-thinking-that-acute-heart-failure-is-a-48-hour-illness
#7
EDITORIAL
Peter A McCullough
Trials of novel therapies for acute heart failure (HF) have followed a convention of short term, most commonly a 48-hour infusion of parenteral therapy compared with placebo or an active drug in a randomized, double-blind study design. Such trials include OPTIME-CHF, SURVIVE, VERITAS, PROTECT, ASCEND-HF, TRUE-HF, and RELAX-AHF-2. This article reviews how this practice in trials began and summarizes the reasons why such a brief exposure of any novel therapy has failed to reduce the end points of rehospitalization or death...
August 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28454809/day-vs-night-does-time-of-presentation-matter-in-acute-heart-failure-a-secondary-analysis-from-the-relax-ahf-trial
#8
RANDOMIZED CONTROLLED TRIAL
Peter S Pang, John R Teerlink, Leandro Boer-Martins, Claudio Gimpelewicz, Beth A Davison, Yi Wang, Adriaan A Voors, Thomas Severin, Piotr Ponikowski, Tsushung A Hua, Barry H Greenberg, Gerasimos Filippatos, G Michael Felker, Gad Cotter, Marco Metra
BACKGROUND: Signs and symptoms of heart failure can occur at any time. Differences between acute heart failure (AHF) patients who present at nighttime vs daytime and their outcomes have not been well studied. Our objective was to determine if there are differences in baseline characteristics and clinical outcomes between AHF patients presenting during daytime vs nighttime hours within an international, clinical trial. METHODS: This is a post hoc analysis of the RELAX AHF trial, which randomized 1,161 AHF patients to serelaxin vs placebo, both in addition to usual AHF therapy...
May 2017: American Heart Journal
https://www.readbyqxmd.com/read/28452195/serelaxin-in-addition-to-standard-therapy-in-acute-heart-failure-rationale-and-design-of-the-relax-ahf-2-study
#9
RANDOMIZED CONTROLLED TRIAL
John R Teerlink, Adriaan A Voors, Piotr Ponikowski, Peter S Pang, Barry H Greenberg, Gerasimos Filippatos, G Michael Felker, Beth A Davison, Gad Cotter, Claudio Gimpelewicz, Leandro Boer-Martins, Margaret Wernsing, Tsushung A Hua, Thomas Severin, Marco Metra
Patients admitted for acute heart failure (AHF) experience high rates of in-hospital and post-discharge morbidity and mortality despite current therapies. Serelaxin is recombinant human relaxin-2, a hormone with vasodilatory and end-organ protective effects believed to play a central role in the cardiovascular and renal adaptations of human pregnancy. In the phase 3 RELAX-AHF trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for AHF. Compared to placebo, serelaxin also reduced worsening heart failure (WHF) by 47% through day 5 and both all-cause and cardiovascular mortality by 37% through day 180...
June 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28217307/worse-prognosis-of-real-world-patients-with-acute-heart-failure-from-the-czech-ahead-registry-in-comparison-to-patients-from-the-relax-ahf-trial
#10
Jindrich Spinar, Jiri Jarkovsky, Lenka Spinarova, Jiri Vitovec, Ales Linhart, Petr Widimsky, Roman Miklik, Kamil Zeman, Jan Belohlavek, Filip Malek, Cestmir Cihalik, Jiri Spac, Marian Felsoci, Petr Ostadal, Ladislav Dusek, Jiri Kettner, Jan Vaclavik, Simona Littnerova, Zdeněk Monhart, Josef Malek, Jiri Parenica
AIMS: The randomized clinical trial RELAX-AHF demonstrated a positive effect of vasodilator therapy with serelaxin in the treatment of AHF patients. The aim of our study was to compare clinical characteristics and outcomes of patients from the AHEAD registry who met criteria of the RELAX-AHF trial (relax-comparable group) with the same characteristics and outcomes of patients from the AHEAD registry who did not meet those criteria (relax-non-comparable group), and finally with characteristics and outcomes of patients from the RELAX-AHF trial...
February 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/28150186/serelaxin-in-acute-heart-failure-patients-with-and-without-atrial-fibrillation-a-secondary-analysis-of-the-relax-ahf-trial
#11
RANDOMIZED CONTROLLED TRIAL
Gerasimos Filippatos, Dimitrios Farmakis, Marco Metra, Gad Cotter, Beth A Davison, G Michael Felker, Barry H Greenberg, Tsushung A Hua, Peter S Pang, Piotr Ponikowski, Min Qian, Thomas A Severin, Adriaan A Voors, John R Teerlink
BACKGROUND: Atrial fibrillation (AFib) is a common comorbidity in HF and affects patients' outcome. We sought to assess the effects of serelaxin in patients with and without AFib. METHODS: In a post hoc analysis of the RELAX-AHF trial, we compared the effects of serelaxin on efficacy end points, safety end points and biomarkers in 1161 patients with and without AFib on admission electrocardiogram. RESULTS: AFib was present in 41.3% of patients...
June 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28133908/a-multimarker-multi-time-point-based-risk-stratification-strategy-in-acute-heart-failure-results-from-the-relax-ahf-trial
#12
Biniyam G Demissei, Gad Cotter, Margaret F Prescott, G Michael Felker, Gerasimos Filippatos, Barry H Greenberg, Peter S Pang, Piotr Ponikowski, Thomas M Severin, Yi Wang, Min Qian, John R Teerlink, Marco Metra, Beth A Davison, Adriaan A Voors
AIMS: We evaluated the added prognostic value of a multi-time point-based multimarker panel of biomarkers in patients with acute heart failure (AHF). METHODS AND RESULTS: Seven circulating biomarkers [NT-proBNP, high sensitivity cardiac troponin T (hs-cTnT), soluble ST2 (sST2), growth differentiation factor 15 (GDF-15), cystatin-C, galectin-3, and high sensitivity C-reactive protein (hs-CRP)] were measured at baseline and on days 2, 5, 14, and 60 in 1161 patients enrolled in the RELAX-AHF trial...
January 30, 2017: European Journal of Heart Failure
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-design-and-rationale-of-relax-ahf-asia-trial
#13
RANDOMIZED CONTROLLED TRIAL
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, but 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, with the use of novel assessments...
January 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/27727514/serelaxin-in-acute-heart-failure-most-recent-update-on-clinical-and-preclinical-evidence
#14
REVIEW
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 healthcare costs and is 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 nonpregnant women and men...
February 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/27104862/potential-new-drug-treatments-for-congestive-heart-failure
#15
REVIEW
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-patients-with-acute-heart-failure-at-lower-risk-for-adverse-outcomes-an-exploratory-analysis-from-the-relax-ahf-trial
#16
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
#17
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
#18
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
#19
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
#20
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
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