Low-Dose Dopamine or Low-Dose Nesiritide in Acute Heart Failure With Renal Dysfunction The ROSE Acute Heart Failure Randomized Trial

• Type of Material: Article
• Authors: Horng H. Chen, Mayo Clinic; Kevin J. Anstrom, Duke Clinical Research Institute; Michael M. Givertz, Brigham & Women's Hospital; Lynne W. Stevenson, Brigham & Women's Hospital; Marc J. Semigran, Massachusetts General Hospital; Steven R. Goldsmith, Hennepin County Medical Center; Bradley A. Bart, Hennepin County Medical Center; David A. Bull, University of Utah; Josef Stehlik, University of Utah; Martin M. LeWinter, University of Vermont; Marvin A. Konstam, Tufts Medical Center; Gordon S. Huggins, Tufts Medical Center; Jean L. Rouleau, University of Montreal; Eileen O'Meara, University of Montreal; W. H. Wilson Tang, Cleveland Clinic; Randall C. Starling, Cleveland Clinic; Javed Butler, Emory University; Anita Deswal, Michael E DeBakey VA Medical Center; G. Michael Felker, Duke University; Christopher M. O'Connor, Duke University
• Language: English
• Date: 2013-12-18
• Publisher: American Medical Association (AMA): JAMA
• Publication Version: Final Published Version
• Copyright Statement: Copyright 2013 American Medical Association. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1001/jama.2013.282190
• Title of Journal or Parent Work: Journal of the American Medical Association
• ISSN: 0098-7484
• Volume: 310
• Issue: 23
• Start Page: 2533
• End Page: 2543
• Grant/Funding Information: This work is also supported by the National Center for Advancing Translational Sciences (NCATS): UL1TR000454, UL1 TR000135, UL1RR025008, UL1TR 000439; and the National Institute on Minority Health and Health Disparities (NIMHD): 8 U54 MD007588.; Supported by grants from the NHLBI: Coordinating Center: U10 HL084904;; Regional Clinical Centers: U01 HL084861; U10 HL110312; U109 HL110337; U01 HL084889; U01HL084890; U01 HL084891; U10 HL110342; U10 HL110262; U01 HL084931; U10 HL110297;U10 HL110302; U10 HL110309; U10 HL110336; U10 HL110338.
• Keywords: RELAX-AHF; General & Internal Medicine; Science & Technology; Medicine, General & Internal; SERELAXIN; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Medicine and Surgery

Abstract

IMPORTANCE: Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested. OBJECTIVE: To test the 2 independent hypotheses that, compared with placebo, addition of low-dose dopamine (2 μg/kg/min) or low-dose nesiritide (0.005 μg/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, placebo-controlled clinical trial (Renal Optimization Strategies Evaluation [ROSE]) of 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73m2), randomized within 24 hours of admission. Enrollment occurred from September 2010 to March 2013 across 26 sites in North America. INTERVENTIONS: Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategy. Within each strategy, participants were randomized in a double-blind, 2:1 ratio to active treatment or placebo. The dopamine (n = 122) and nesiritide (n = 119) groups were independently compared with the pooled placebo group (n = 119). MAIN OUTCOMES AND MEASURES: Coprimary end points included 72-hour cumulative urine volume (decongestion end point) and the change in serum cystatin C from enrollment to 72 hours (renal function end point). RESULTS: Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95%CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830 ; difference, 229 mL; 95%CI, -714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12mg/L; 95%CI, 0.06-0.18 vs placebo, 0.11mg/L; 95%CI, 0.06-0.16; difference, 0.01; 95%CI, -0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95%CI, 8014-9134 vs placebo, 8296 mL; 95%CI, 7762-8830; difference, 279 mL; 95%CI, -618 to 1176 mL; P = .49) or on the change in cystatin C level (nesiritide, 0.07mg/L; 95%CI, 0.01-0.13 vs placebo, 0.11mg/L; 95%CI, 0.06-0.16; difference, -0.04; 95%CI, -0.13 to 0.05; P = .36). Compared with placebo, there was no effect of low-dose dopamine or nesiritide on secondary end points reflective of decongestion, renal function, or clinical outcomes. CONCLUSIONS In participants with acute heart failure and renal dysfunction, neither low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy.