Effects of serelaxin in patients with acute heart failure

49siSerelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure.openopenMetra M.; Teerlink J.R.; Cotter G.; Davison B.A.; Felker G.M.; Filippatos G.; Greenberg B.H.; Pang P.S.; Ponikowski P.; Voors A.A.; Adams K.F.; Anker S.D.; Arias-Mendoza A.; Avendano P.; Bacal F.; Bohm M.; Bortman G.; Cleland J.G.F.; Cohen-Solal A.; Crespo-Leiro M.G.; Dorobantu M.; Echeverria L.E.; Ferrari R.; Goland S.; Goncalvesova E.; Goudev A.; Kober L.; Lema-Osores J.; Levy P.D.; McDonald K.; Manga P.; Merkely B.; Mueller C.; Pieske B.; Silva-Cardoso J.; Spinar J.; Squire I.; Stepinska J.; Van Mieghem W.; Von Lewinski D.; Wikstrom G.; Yilmaz M.B.; Hagner N.; Holbro T.; Hua T.A.; Sabarwal S.V.; Severin T.; Szecsody P.; Gimpelewicz C.Metra, M.; Teerlink, J. R.; Cotter, G.; Davison, B. A.; Felker, G. M.; Filippatos, G.; Greenberg, B. H.; Pang, P. S.; Ponikowski, P.; Voors, A. A.; Adams, K. F.; Anker, S. D.; Arias-Mendoza, A.; Avendano, P.; Bacal, F.; Bohm, M.; Bortman, G.; Cleland, J. G. F.; Cohen-Solal, A.; Crespo-Leiro, M. G.; Dorobantu, M.; Echeverria, L. E.; Ferrari, R.; Goland, S.; Goncalvesova, E.; Goudev, A.; Kober, L.; Lema-Osores, J.; Levy, P. D.; Mcdonald, K.; Manga, P.; Merkely, B.; Mueller, C.; Pieske, B.; Silva-Cardoso, J.; Spinar, J.; Squire, I.; Stepinska, J.; Van Mieghem, W.; Von Lewinski, D.; Wikstrom, G.; Yilmaz, M. B.; Hagner, N.; Holbro, T.; Hua, T. A.; Sabarwal, S. V.; Severin, T.; Szecsody, P.; Gimpelewicz, C

Effects of serelaxin in patients with acute heart failure

BACKGROUND Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. Copyright © 2019 Massachusetts Medical Society

Comparison of fatal or irreversible events with extended-duration betrixaban versus standard dose enoxaparin in acutely Ill medical patients: An APEX trial substudy

Background-Extended-duration betrixaban showed a significant reduction in venous thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study). Given the variable clinical impact of different efficacy and safety events, one approach to assess net clinical outcomes is to include only those events that are either fatal or cause irreversible harm. Methods and Results-This was a post hoc analysis of the APEX trial-a multicenter, double-blind, randomized controlled trial comparing extended-duration betrixaban versus standard-of-care enoxaparin. A composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and ischemic stroke) was evaluated in a time-to-first event analysis. In patients with positive D-dimer results, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction, 1.26%; number needed to treat, 79 [P=0.033]) and at study end at 77 days (6.27% versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed to treat, 52 [P=0.005]) versus enoxaparin. In all patients, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio, 0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [P=0.006]) and 77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%; number needed to treat, 65 [P=0.002]). Conclusions-Among hospitalized medically ill patients, extended-duration betrixaban demonstrated an 48 30% reduction in fatal or irreversible ischemic or bleeding events compared with standard-duration enoxaparin. A total of 65 patients would require treatment with betrixaban to prevent 1 fatal or irreversible event versus enoxaparin