Challenging a Widespread 'Truth'
At 72 hours, no demonstrable differences in outcomes were seen. Urine output was greater than 8 L in those who received dopamine, those who received nesiritide, and those who received placebo. The difference between dopamine and placebo groups was only 229 mL (P = .59). The difference between nesiritide and placebo groups was similarly small at 279 mL (P = .49). In addition, the change in cystatin C from baseline was also small and similar for the active treatment arms. Cystatin C increased by a mean of 0.11 mg/L from baseline in the placebo group, 0.12 mg/L in the dopamine group, and 0.07 mg/L in the nesiritide group.
Likewise, few differences were seen in secondary endpoints. Fewer patients receiving dopamine than placebo stopped study drug due to hypotension (1 vs 12; P < 0.001), but more patients receiving dopamine stopped the drug due to tachycardia (8 vs 1; P < .001). Treatment failures were similar: 30% in the dopamine arm vs 28% in the placebo arm. More patients in the nesiritide arm stopped study drug due to hypotension (22 vs 12 in the placebo arm; P = .07). Of note, treatment failures reached 40% in the nesiritide group vs 28% of those receiving placebo (P = .04). Treatment failure was defined as the development of cardiorenal syndrome, worsening or persistent heart failure, significant hypotension, or tachycardia requiring discontinuation of study drug.
When variations in 72-hour urine output or cystatin C were examined among subgroups based on age, baseline blood urea nitrogen, baseline cystatin C, baseline eGFR, ejection fraction, and systolic blood pressure, patients with an ejection fraction of >50% who received placebo had a greater urinary volume at 72 hours than those who received dopamine (P = .01). Of interest, in this subgroup, a trend toward a greater urinary volume was also seen among those receiving placebo compared with those receiving nesiritide (P = .06). Given the multiple subgroups examined, these differences need to be interpreted with caution.
This study boldly tested what was taught as truth for decades: that lower-dose dopamine assists in the diuresis of patients with heart failure. The conduct of this trial, as with many that seek to provide evidence for what is considered widespread standard of care, must have been difficult to accomplish. This important study shows that no benefit exists with this therapy (in this group of patients) but also defines the standard of care and examines where the unmet medical need exists.
It is too bad that we cannot speak directly to the renal arteries and influence renal blood flow. Perhaps now that we know what does not work, we can continue to explore treatment strategies that will allow us to link better perfusion with diuresis.
Abstract
Study Results
At 72 hours, no demonstrable differences in outcomes were seen. Urine output was greater than 8 L in those who received dopamine, those who received nesiritide, and those who received placebo. The difference between dopamine and placebo groups was only 229 mL (P = .59). The difference between nesiritide and placebo groups was similarly small at 279 mL (P = .49). In addition, the change in cystatin C from baseline was also small and similar for the active treatment arms. Cystatin C increased by a mean of 0.11 mg/L from baseline in the placebo group, 0.12 mg/L in the dopamine group, and 0.07 mg/L in the nesiritide group.
Likewise, few differences were seen in secondary endpoints. Fewer patients receiving dopamine than placebo stopped study drug due to hypotension (1 vs 12; P < 0.001), but more patients receiving dopamine stopped the drug due to tachycardia (8 vs 1; P < .001). Treatment failures were similar: 30% in the dopamine arm vs 28% in the placebo arm. More patients in the nesiritide arm stopped study drug due to hypotension (22 vs 12 in the placebo arm; P = .07). Of note, treatment failures reached 40% in the nesiritide group vs 28% of those receiving placebo (P = .04). Treatment failure was defined as the development of cardiorenal syndrome, worsening or persistent heart failure, significant hypotension, or tachycardia requiring discontinuation of study drug.
When variations in 72-hour urine output or cystatin C were examined among subgroups based on age, baseline blood urea nitrogen, baseline cystatin C, baseline eGFR, ejection fraction, and systolic blood pressure, patients with an ejection fraction of >50% who received placebo had a greater urinary volume at 72 hours than those who received dopamine (P = .01). Of interest, in this subgroup, a trend toward a greater urinary volume was also seen among those receiving placebo compared with those receiving nesiritide (P = .06). Given the multiple subgroups examined, these differences need to be interpreted with caution.
Viewpoint
This study boldly tested what was taught as truth for decades: that lower-dose dopamine assists in the diuresis of patients with heart failure. The conduct of this trial, as with many that seek to provide evidence for what is considered widespread standard of care, must have been difficult to accomplish. This important study shows that no benefit exists with this therapy (in this group of patients) but also defines the standard of care and examines where the unmet medical need exists.
It is too bad that we cannot speak directly to the renal arteries and influence renal blood flow. Perhaps now that we know what does not work, we can continue to explore treatment strategies that will allow us to link better perfusion with diuresis.
Abstract
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