In the Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE AHF) trial , patients with acute decompensated heart failure (ADHF) and renal impairment were randomized in a double-blind fashion to 72 hours of low-dose dopamine (2 mcg/kg/min), low-dose nesiritide (0.005 mcg/kg/min), or placebo. Patients were eligible for enrollment if they had at least one sign and symptom of ADHF (irrespective of ejection fraction) and an estimated glomerular filtration rate (eGFR) of 15-60 mL/min/1.73 m2. Baseline characteristics were similar between the three groups with a median systolic blood pressure of 115 mmHg, median ejection fraction (EF) of 33% (over two-thirds with EF < 50%), and eGFR of 42 mL/min/1.73 m2.
Low-dose dopamine failed to produce a difference in the co-primary endpoints of cumulative urine output (UOP) or change in cystatin C at 72 hours compared to placebo (differences in UOP of 8254 mL and 8296 mL, respectively, p = 0.59). Drug discontinuation was similar between the two groups, although low-dose dopamine was more likely to be discontinued for tachycardia (7.2% vs. 0.9% with placebo, p < 0.001) while placebo was discontinued more frequently for hypotension (10.4% vs. 0.9% with low-dose dopamine, p < 0.001). Likewise, low-dose nesiritide also failed to confer significant differences in the co-primary endpoint (differences in UOP of 8574 mL and 8296 mL with placebo, p < 0.49). Compared to placebo, hypotension was more common in the low-dose nesiritide group (18.8% vs. 10.4% with placebo, p = 0.07). Results for the co-primary endpoints were similar across subgroups with the exception of EF. Compared to dopamine, patients with preserved EF tended to do better with placebo (p = 0.01 for interaction). In contrast, nesiritide appeared to benefit those with reduced EF, although this difference was not statistically significant. No differences in clinical endpoints (e.g., symptom relief, death, rehospitalization) were observed between any of the groups.
Those who follow my blog know that I am no fan of using low-dose dopamine for the purposes of renoprotection in ADHF (previous entries here and here). While I am not opposed to its use as a mixed inotrope/vasopressor (i.e., for patients in whom peripheral vasodilation from a traditional inotrope might compromise hemodynamics), the renoprotective properties of low-dose dopamine have been widely discredited . Given the lack of benefit observed in ROSE AHF, hopefully this myth has been debunked once and for all. Importantly, dopamine not only failed to produce a significant difference in the co-primary endpoints; it also resulted in lower rates of hypotension and higher rates of tachycardia, indicating that even at doses as low as 2 mcg/kg/min, dopamine is not entirely selective for renal vascular beds.
Unfortunately, a signal of differential response between those with reduced versus preserved EF was observed (although not statistically significant), which may provide just enough justification to continue evaluating this approach in select subgroups. Although the inclusion of a low-dose nesiritide arm in this study was an interesting hypothesis, the fact that it did not produce a meaningful difference in outcomes is not altogether unsurprising.
Neither low-dose dopamine nor low-dose nesiritide provide renoprotective effects in patients with ADHF and renal impairment.
- Chen HH, Anstrom KJ, Givertz MM, Stevenson LW, Semigran MJ, Goldsmith SR, et al. Low-Dose Dopamine or Low-Dose Nesiritide in Acute Heart Failure With Renal Dysfunction: The ROSE Acute Heart Failure Randomized Trial. JAMA J Am Med Assoc. 2013 Nov 18;
- Cicci JD, Reed BN, McNeely EB, Oni-Orisan A, Patterson JH, Rodgers JE. Acute Decompensated Heart Failure: Evolving Literature and Implications for Future Practice. Pharmacotherapy. 2013 Nov 11;