DALLAS, TX — As part of the enduring quest for drugs that can safely improve decongestion in diuretic-managed acute heart failure (AHF), a randomized trial separately testing low-dose infusions of dopamine and nesiritide (NatreCor, Scios/Johnson & Johnson) in AHF patients with renal dysfunction found that neither is likely to answer the call[1].
In the Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE AHF) trial, which randomized 360 patients hospitalized with AHF and renal dysfunction, neither drug regimen—added to standard management including loop diuretics—boosted decongestion or improved kidney function over 72 hours compared with placebo. Nor did either drug treatment favorably alter clinical outcomes at either two or six months.
All that was despite evidence from small studies suggesting the opposite might be true for both regimens and even current practice patterns, in which either drug at low dosages is sometimes used in such patients, according to Dr Horng H Chen (Mayo Clinic, Rochester, MN).
Dr Horng H Chen
Chen, who spoke at a press briefing on the trial here at the American Heart Association (AHA) 2013 Scientific Sessions , is lead author on its publication, released today in the Journal of the American Medical Association; ROSE-AHF was one of the late-breaking clinical trials presented at the meeting today.
The study shows that dopamine shouldn't be used routinely in acute HF, according to Chen. At higher dosages it could sometimes be used for its inotropic effects, but that wasn't explored in ROSE-AHF. "So I think the use of dopamine will have to be individualized according to physician assessment of the patient."
Dr Marco Metra
To heartwire , Dr Marco Metra (University of Brescia, Italy) said the trial should lead to less use of dopamine in patients with AHF, which is currently "done too often as a routine at some centers." He said the drug, usually at low dosages, is used in AHF at about 3% to 5% of US hospitals but as many as 10% to 15% of European centers, especially in Italy.
Nesiritide isn't generally available to European physicians but is used for AHF in 5% to 10% of US hospitals, according to Metra, who was the assigned discussant for Chen's presentation of the trial.
Dr Mark A Creager (Brigham and Women's Hospital, Boston, MA), who wasn't connected with the trial, said to heartwire that "based on this trial and trials that have preceded it, there has been really insufficient evidence to support the use of nesiritide in most patients with heart failure."
He said he hopes ROSE-AHF gets clinicians to hold back on using either dopamine or nesiritide in patients like those in the trial. "This is a negative study for this population, patients with acute heart failure with impairment in renal function. And although the rationale for the study was outstanding, they were not shown to be effective," Creager said.
The patients from 26 US sites were openly randomized to two cohorts, one that would test the dopamine strategy and another that would test the nesiritide strategy. In each cohort, patients were randomized in a 2:1 ratio and in double-blind fashion to receive the active drug or placebo. Then both placebo groups were pooled into one that totaled 119 patients, with which the dopamine (n=122) and nesiritide (n=119) groups were separately compared.
Dopamine was infused at 2 µg/kg/min, and in the other group, nesiritide was infused at 0.005 µg/kg/min without a bolus. All patients received open-label, intravenous loop-diuretic treatment, but further diuretics and other medications were allowed at physicians' discretion. All patients followed a 2000-mg/day sodium diet and restricted fluids to 2000 mL/day.
Neither drug had a significant effect on 72-hour cumulative urine volume or change in serum cystatin-C levels from enrollment to 72 hours, the co–primary end points reflecting decongestion and change in renal function, respectively.
The two groups did not differ significantly in total dosage of diuretics used or 72-hour fluid intake.
Nor did they differ in risk of death or HF readmission at 60 days or in mortality at 180 days.
"I think there are some caveats" about using the two agents in AHF, Creager said. "There are some situations, [such as] when someone has acute heart failure and compromised blood pressure, [when] you might individualize and use low-dose dopamine. But I don't think people should be impulsive about starting these drugs."
The study was funded by the National Heart, Lung, and Blood Institute. Chen reports serving on the board of Zumbro Discovery (as cofounder), receiving grants from Scios, and receiving royalties from Nile Therapeutics, Anexon, and UpToDate. Disclosures for the coauthors are listed in the paper.
Heartwire from Medscape © 2013
Cite this: Dopamine, Nesiritide Unhelpful in Kidney-Compromised Acute Heart Failure: ROSE-AHF Trial - Medscape - Nov 18, 2013.
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