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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. RELAX-AHF-2 ( ClinicalTrials.gov NCT01870778) is designed to confirm serelaxin's effect on these clinical outcomes. RELAX-AHF-2 is a multicentre, randomized, double-blind, placebo-controlled, event-driven, phase 3 trial enrolling ∼6800 patients hospitalized for AHF with dyspnoea, congestion on chest radiograph, increased natriuretic peptide levels, mild-to-moderate renal insufficiency, and systolic blood pressure ≥125 mmHg. Patients are randomized within 16 h of presentation to 48 h intravenous infusions of serelaxin (30 µg/kg/day) or placebo, both in addition to standard of care treatments. The primary objectives are to demonstrate that serelaxin is superior to placebo in reducing: (i) 180 day cardiovascular death, and (ii) occurrence of WHF through day 5. Key secondary endpoints include 180 day all-cause mortality, composite of 180 day combined cardiovascular mortality or heart failure/renal failure rehospitalization, and in-hospital length of stay during index AHF. The results from RELAX-AHF-2 will provide data on the potential beneficial effect of serelaxin on cardiovascular mortality and WHF in selected patients with AHF. [ABSTRACT FROM AUTHOR]

Question: What are the relative efficacy and safety of warfarin and aspirin in patients with heart failure who are in sinus rhythm? Methods Design: Randomized controlled trial (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction [WARCEF] trial). ClinicalTrials.gov NCT00041938. Allocation: {Concealed}*.† Blinding: Blinded† (patients, clinicians, {data collectors, safety committee}*, and outcome assessors). Follow-up period:  6 years (mean 3.5 y). Setting: 168 centers in the USA, Canada, Argentina, and Europe. Patients: 2305 adults =" src="ge9.gif"/> 18 years of age (mean age 61 y, 80% men) who had a left ventricular ejection fraction (LVEF)  35% and normal sinus rhythm, and planned treatment with a β-blocker, angiotensin-converting enzyme inhibitor, or hydralazine and nitrates. Exclusion criteria included modified Rankin score > 4, medical conditions with high risk for cardiac embolism, clear indication for warfarin or aspirin, or contraindication to warfarin. Patients in New York Heart Association class I were eligible but could not comprise > 20% of randomized patients. Intervention: Active warfarin (with target international normalized ratio 2.0 to 3.5) plus aspirin placebo (n = 1142), or aspirin, 325 mg/d, plus warfarin placebo (n = 1163). Outcomes: Primary composite endpoint of ischemic stroke, intracerebral hemorrhage (ICH), or death. Secondary outcome was a composite of ischemic stroke, ICH, death, myocardial infarction, or hospitalization for heart failure. The safety outcome was a composite of ischemic stroke, ICH, death, or intracranial hemorrhage. The trial had 69% power to detect a relative hazard reduction of 17.8% in the primary outcome and 83% power for the secondary outcome. Patient follow-up: {93%}* (96% for vital status; intention-to-treat analysis). Main results: Enrolment was stopped early because of slow recruitment. Groups did not differ for the primary composite outcome or any of its components except for ischemic stroke (Table). Groups also did not differ for the secondary or safety composite endpoints (Table). Conclusion: In patients with heart failure who are in sinus rhythm, warfarin and aspirin did not differ for a composite of death or ischemic or hemorrhage outcomes. [ABSTRACT FROM AUTHOR]

Background: Acute heart failure (AHF) remains a major public health burden with a high prevalence and poor prognosis. Relaxin is a naturally occurring peptide hormone that increases cardiac output, arterial compliance, and renal blood flow during pregnancy. The RELAX-AHF-1 study will evaluate the effect of RLX030 (recombinant form of human relaxin 2) on symptom relief and clinical outcomes in patients with AHF., Methods: The protocol includes a completed phase 2 234-patient dose-finding study (Pre-RELAX-AHF) and an ongoing phase 3 1,160-patient trial (RELAX-AHF-1). Patients with AHF and systolic blood pressure >125 mm Hg are randomized within 16 hours of presentation to a 48-hour IV infusion of RLX030 or placebo. The 30 μg/kg per day dose of RLX030 was chosen for RELAX-AHF-1 based on effects on dyspnea, clinical outcomes, and safety observed in Pre-RELAX-AHF. Primary efficacy end points in RELAX-AHF-1 are (1) the area under the curve of change of the dyspnea Visual Analog Scale from baseline through day 5 and (2) whether the patient reports moderately to markedly better dyspnea at 6, 12, and 24 hours. Secondary efficacy end points include days alive and out of the hospital through day 60 and cardiovascular death or rehospitalization for heart failure or renal failure through day 60. Patients will be followed up through day 180 for mortality. As of September 19, 2011, 978 patients have been enrolled., Conclusions: Pre-RELAX-AHF results suggested that infusion of RLX030 may accelerate dyspnea relief and improve prognosis in patients hospitalized with AHF. RELAX-AHF-1 will further evaluate these effects., (Copyright © 2012 Mosby, Inc. All rights reserved.)