Low-Dose Dopamine or Low-Dose Nesiritide in Acute Heart Failure With Renal Dysfunction

Abstract

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/1.73 m 2 ), 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, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/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, 8296mL; 95% CI, 7762-8830; difference, 279 mL; 95% CI, −618 to 1176 mL; P = .49) or on the change in cystatin C level (nesiritide, 0.07 mg/L; 95% CI, 0.01-0.13 vs placebo, 0.11 mg/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 RELEVANCEIn 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.

Pro‐Inflammatory Biomarkers in Stable Versus Acutely Decompensated Heart Failure With Preserved Ejection Fraction

“…We measured IL‐6, TNF‐α, and hs‐CRP and PTX3 in age and sex‐matched cohorts of HFpEF patients from 3 prospective, placebo‐controlled, randomized clinical trials conducted by the NHLBI Heart Failure Research Network, RELAX (Effect of Phosphodiesterase‐5 Inhibition on Exercise Capacity and Clinical Status in Heart Failure with Preserved Ejection Fraction),37 DOSE (Diuretic Strategies in Patients With Acute Decompensated Heart Failure)38 and ROSE (Renal Optimization Strategies Evaluation) 39. RELAX included S‐HFpEF patients while DOSE and ROSE included acutely decompensated HF (ADHF) patients with both HFrEF and HFpEF.…”

Angiotensin Receptor Neprilysin Inhibition in Heart Failure: Mechanistic Action and Clinical Impact

“…26 Low-dose nesiritide as renal adjuvant therapy in patients admitted with ADHF and concomitant renal dysfunction was evaluated in the recently completed Renal Optimization Strategies Evaluation (ROSE) trial. 27 Despite the theoretic benefit of enhancing diuresis and preserving renal function, patients receiving nesiritide had no difference in decongestion or renal function at 72 hours compared with placebo. These data have limited the use of nesiritide to adjunctive therapy with diuretics for dyspnea relief in acute HF.…”

Cardiorenal syndrome or renocardial syndrome:A review

“…A report from the DAD-HF trial of 60 patients with acute decompensated HF found that the combination of dopamine 5 mcg/kg/min plus lowdose furosemide (5mg/h continuous infusion) produced similar urine output as high-dose furosemide (20 mg/h) with reduced risk of worsening renal function (defined as rise in serum creatinine of more than 0.3 mg/dl from baseline to 24 hours; 7 versus 30 percent) [78]. The Renal Optimization Strategies Evaluation (ROSE) trial also tested the hypothesis of whether low-dose dopamine (2mcg/kg/min) (n= 122) would improve urine output and renal function compared to placebo (n= 119) among patients hospitalized with HF and concomitant renal disease [79]. Low-dose dopamine did not improve decongestion or increase renal function when added to diuretic therapy.…”

“…The largest trial, ASCEND-HF, found no change in the outcome of worsening renal function with nesiritide therapy (continuous infusion at 0.01 µg/kg/min with an optional initial loading dose of 2 µg/kg) [82,83]. Similarly, the Renal Optimization Strategies Evaluation (ROSE) trial found that low-dose nesiritide (0.005 µg/kg/min without bolus for 72 h) did not improve decongestion or alter renal function when added to diuretic therapy [79].…”