Browsing by Author "Filippatos, G."

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    Effects of Serelaxin in Patients with Acute Heart Failure
    (Massachusetts Medical Society, 2019-08) 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.; Avendaño, P.; Bacal, F.; Böhm, M.; Bortman, G.; Cleland, J. G. F.; Cohen-Solal, A.; Crespo-Leiro, M. G.; Dorobantu, M.; Echeverría, L. E.; Ferrari, R.; Goland, S.; Goncalvesová, E.; Goudev, A.; Køber, L.; Lema‑Osores, J.; Levy, P. D.; McDonald, K.; Manga, P.; Merkely, B.; Mueller, C.; Pieske, B.; Silva-Cardoso, J.; Špinar, J.; Squire, I.; Stępińska, J.; Van Mieghem, W.; von Lewinski, D.; Wikström, G.; Yilmaz, M. B.; Hagner, N.; Holbro, T.; Hua, T. A.; Sabarwal, S. V.; Severin, T.; Szecsödy, P.; Gimpelewicz, C.; Emergency Medicine, School of Medicine
    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.
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    POS-829 Incidence and predictors of hyperkalaemia in patients with CKD and T2D in the FIDELIO-DKD trial
    (Elsevier, 2021) Agarwal, R.; Joseph, A.; Rossing, P.; Pitt, B.; Anker, D. S.; Filippatos, G.; Ruilope, M. L.; Kolkhof, P.; Scott, C.; Lawatscheck, R.; Bakris, L. G.; Medicine, School of Medicine
    Introduction: Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) have an increased risk of hyperkalaemia. Finerenone, a novel, selective, nonsteroidal, mineralocorticoid receptor antagonist, reduced the incidence of kidney and cardiovascular events in patients with CKD and T2D in the FIDELIO-DKD trial. This post hoc analysis describes the incidence and predictors of hyperkalaemia in FIDELIO-DKD. Methods: FIDELIO-DKD was a phase III, multicentre, double-blind trial that randomised 5734 patients (1:1) to finerenone or placebo. Patients with CKD, T2D and serum potassium ([K+]) ≤4.8 mmol/l at the run-in and screening visits, and treated with optimised renin–angiotensin system blockade were included. CKD was defined as a urine albumin-to-creatinine ratio (UACR) ≥30–<5000 mg/g and an estimated glomerular filtration rate (eGFR) ≥25–<75 ml/min/1.73 m2. Initial dosing of study drug (10 mg or 20 mg once daily [od]) was based on eGFR at screening. During the trial, study drug dosing was based on serum [K+] levels and eGFR changes, which were monitored at every study visit; the study drug was temporarily withheld if [K+] >5.5 mmol/l and restarted at 10 mg od when [K+] ≤5.0 mmol/l. In this safety analysis, hyperkalaemia was defined as an investigator-reported adverse event (AE) or by serum [K+] levels (>5.5 and >6.0 mmol/l); events were considered treatment-emergent if they occurred after the start of study drug administration and until 3 days after any interruption of study drug. Multivariate Cox proportional hazards regression was used to examine associations between baseline characteristics and first post-baseline treatment-emergent [K+] >5.5 or >6.0 mmol/l, adjusting for treatment assignment and baseline covariates chosen a priori based on clinical factors known to affect serum [K+]. A p‑value <0.05 was used to determine a significant association. Results: At baseline, 769/5658 (13.6%) and 390/5658 (6.9%) patients had [K+] >4.8 mmol/l and >5.0 mmol/l, respectively. After a median follow-up of 2.6 years, 44/2827 (1.6%) patients in the finerenone group and 12/2831 (0.4%) patients in the placebo group experienced a treatment-emergent hyperkalaemia-related serious AE. In the finerenone group, 64/2827 (2.3%) patients permanently discontinued the study drug due to hyperkalaemia, compared with 25/2831 (0.9%) patients in the placebo group. In total, 597/2785 (21.4%) and 256/2775 (9.2%) patients in the finerenone and placebo groups, respectively, had a treatment-emergent [K+] >5.5 mmol/l, while 126/2802 (4.5%) and 38/2796 (1.4%) patients, respectively, had a treatment-emergent [K+] >6.0 mmol/l. Selected baseline characteristics of patients with vs without any [K+] >5.5 or >6.0 mmol/l during the study are shown in the Table. The results of a multivariate analysis of hyperkalaemia risk factors will be presented. Conclusions: The K+ management protocol implemented in FIDELIO-DKD minimised the clinical impact of hyperkalaemia, as demonstrated by the low frequency of clinically meaningful hyperkalaemia-related serious AEs.