RESUMO
Sleep disorders are a common concomitant comorbidity in patients with heart failure. The aims of our study are to determine the incidence and phenotypic characteristics of sleep apnea in overweight patients with exacerbated heart failure and to assess the degree of involvement of systolic and diastolic function impairment in the individual group. From 100 screened patients with heart failure in our department from 2015 to 2017, 61 met the inclusion criteria and participated in the study. 82% (n = 50) of the patients had obstructive sleep apnea (OSA), and 18% (n = 11) had central sleep apnea (CSA). The CSA group had a significantly lower left ventricular ejection fraction (LVEF) than the OSA group (EF% 49.6 ± 8.5 vs 41.8 ± 11.4; p = 0.013). A negative correlation was found between LVEF and the number of central apnea events (r = -0.52; p < 0.001). More frequent hospitalizations for heart failure (HF) and higher mortality rate were found in the CSA group. Screening for sleep apnea in patients with exacerbated heart failure and obesity is necessary for the complex treatment of these patients.
RESUMO
BACKGROUND: Sabizabulin is an oral, novel microtubule disruptor that has dual antiviral and anti-inflammatory activities in preclinical models. METHODS: A randomized, multicenter placebo-controlled phase 3 clinical trial was conducted with hospitalized patients with moderate to severe Covid-19 who were at high risk for acute respiratory distress syndrome (ARDS) and death. Patients were randomly assigned (2:1) to 9 mg of oral sabizabulin or placebo daily (up to 21 days). The primary end point was all-cause mortality up to day 60. Key secondary end points were days in the intensive care unit (ICU), days on mechanical ventilation, and days in the hospital. RESULTS: A total of 204 patients were randomly assigned to treatment: 134 to sabizabulin and 70 to placebo. Baseline characteristics were similar. Sabizabulin superiority was demonstrated by a planned interim analysis for the first 150 randomized patients. Sabizabulin treatment resulted in a 24.9 percentage point absolute reduction and a 55.2% relative reduction in deaths compared with placebo (odds ratio, 3.23; 95% CI confidence interval, 1.45 to 7.22; P=0.0042). The mortality rate was 20.2% (19 of 94) for sabizabulin versus 45.1% (23 of 51) for placebo. For the key secondary end points, sabizabulin treatment resulted in a 43% relative reduction in ICU days (P=0.0013), a 49% relative reduction in days on mechanical ventilation (P=0.0013), and a 26% relative reduction in days in the hospital (P=0.0277) versus placebo. Adverse and serious adverse events were lower in the sabizabulin group compared with the placebo group. CONCLUSIONS: Sabizabulin treatment resulted in a 24.9% absolute reduction in deaths compared with placebo in hospitalized patients with moderate to severe Covid-19 at high risk for ARDS and death, with a lower incidence of adverse and serious adverse events compared with placebo. (Funded by Veru, Inc.; ClinicalTrials.gov number, NCT04842747.)
