TY - JOUR
T1 - Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction
T2 - The ROSE acute heart failure randomized trial
AU - Chen, Horng H.
AU - Anstrom, Kevin J.
AU - Givertz, Michael M.
AU - Stevenson, Lynne W.
AU - Semigran, Marc J.
AU - Goldsmith, Steven R.
AU - Bart, Bradley A.
AU - Bull, David A.
AU - Stehlik, Josef
AU - LeWinter, Martin M.
AU - Konstam, Marvin A.
AU - Huggins, Gordon S.
AU - Rouleau, Jean L.
AU - O'Meara, Eileen
AU - Tang, W. H.Wilson
AU - Starling, Randall C.
AU - Butler, Javed
AU - Deswal, Anita
AU - Felker, G. Michael
AU - O'Connor, Christopher M.
AU - Bonita, Raphael E.
AU - Margulies, Kenneth B.
AU - Cappola, Thomas P.
AU - Ofili, Elizabeth O.
AU - Mann, Douglas L.
AU - Dávila-Román, Victor G.
AU - McNulty, Steven E.
AU - Borlaug, Barry A.
AU - Velazquez, Eric J.
AU - Lee, Kerry L.
AU - Shah, Monica R.
AU - Hernandez, Adrian F.
AU - Braunwald, Eugene
AU - Redfield, Margaret M.
PY - 2013/12/18
Y1 - 2013/12/18
N2 - 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. CONCLUSION AND RELEVANCE: In participants with acute heart failure and renal dysfunction, neither low-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01132846
AB - 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. CONCLUSION AND RELEVANCE: In participants with acute heart failure and renal dysfunction, neither low-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01132846
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U2 - 10.1001/jama.2013.282190
DO - 10.1001/jama.2013.282190
M3 - Article
C2 - 24247300
AN - SCOPUS:84890369206
SN - 0098-7484
VL - 310
SP - 2533
EP - 2543
JO - JAMA
JF - JAMA
IS - 23
ER -