Patient population

For the present analyses, we studied all patients with available estimated glomerular filtration rate (eGFR) at baseline enrolled in the RELAX-AHF trial. The methods and main results of the study have been published in detail elsewhere [8, 16]. Between October 2009 and February 2012, 1161 acute heart failure patients were randomly assigned within 16 h of presentation to one of the two treatment groups in a 1:1 ratio (serelaxin 30 μg/kg per day or placebo). Eligible patients were adult male or female, hospitalized for acute heart failure, defined as dyspnea at rest or with minimal exertion, pulmonary congestion on chest radiograph and elevated natriuretic peptide levels [brain natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) levels ≥350 or ≥1400 pg/mL, respectively], requiring at least 40 mg intravenous furosemide or its equivalent. Further, patients had to have a systolic blood pressure of >125 mm Hg and mild to moderate renal function (estimated creatinine clearance of 30–75 ml/min/1.73 m²). Key exclusion criteria included signs of active infection, significant pulmonary or valvular disease, acute heart failure due to significant arrhythmias, acute coronary syndrome 45 days prior screening or a troponin level >3 times the level diagnostic of myocardial infarction, and treatment with any other intravenous therapy (except intravenous nitrate at dose of <0.1 mg/kg in patients with systolic blood pressure >150 mmHg). The RELAX-AHF trial was conducted under International Committee on Harmonization Good Clinical Practices and applicable country and local regulations, and approved by the Ethics Committee of each participating site. All patients provided written informed consent. The RELAX-AHF trial is registered at Clinicaltrials.gov, number {"type":"clinical-trial","attrs":{"text":"NCT00520806","term_id":"NCT00520806"}}NCT00520806.