急性心不全において2つの薬剤は腎機能を改善しなかった（LBCT 3/Abstract: 19575）

ROSE AHF：腎機能障害を有する急性心不全においてドーパミンとnesiritideは有用でない
ROSE AHF: Dopamine and Nesiritide unhelpful in kidney-compromised acute heart failure
小規模のスタディで腎機能を改善した2つの薬剤は、2013年American Heart Associationのlate-breaking clinical trialで発表された大規模研究において腎機能障害を有する急性心不全患者にとって有益ではなかった。この結果は同時にJAMAに掲載された。過去の小規模のスタディの結果、低用量ドーパミンまたは低用量nesiritideは急性心不全で入院した患者において、腎機能を改善し尿産生を増加させることにより体液過剰を軽減し得ることが示唆された。Renal Optimization Strategies Evaluation in Acute Heart Failure（ROSE AHF）無作為化トライアルにおいて研究者らは、腎機能障害を有し急性心不全で入院した患者360人のデータを解析した。ドーパミンは2µg/kg/minで静脈内投与され、もう一方の群ではnesiritideがボーラス投与なしの0.005 µg/kg/minで静脈内投与された。全ての患者にオープンラベルで静脈内ループ利尿薬治療が行われたが、他の利尿薬および他の薬剤の追加は医師の裁量に任された。いずれの薬剤も72時間の累積尿量または組み入れから72時間後までの血清シスタチンCの変化、うっ血除去および腎機能の変化を反映する複数一次エンドポイントいずれにも有意な影響を及ぼさなかった。
Full Text

Two drugs that improved kidney function in small studies didn't benefit acute heart failure patients with kidney dysfunction in a larger study presented as a late-breaking clinical trial at the American Heart Association's Scientific Sessions 2013 and published simultaneously in JAMA.

Previous small studies have suggested that low-dose dopamine or low-dose nesiritide could improve kidney function and reduce fluid overload by increasing urine production in patients hospitalized for acute heart failure.

In the Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE AHF) Trial randomized trial, researchers analyzed data on 360 hospitalized acute heart failure patients with renal dysfunction. 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.

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.

"We performed this study because both drugs are already available and there is currently no FDA-approved therapy for enhancing renal function in acute heart failure." said Horng Chen, M.D., professor of medicine at the Mayo Clinic in Rochester, Minn.

The majority of heart failure patients at some stage of the disease develop some degree of renal dysfunction. Conversely, the prevalence of heart failure increases greatly as kidney function deteriorates. The risk is as high as 70 percent for those with end-stage renal disease, according to the National Kidney Foundation.

"There was a suggestion of differential responses to the two study drugs in subsets of patients," Chen said. However, the overall effect wasn't significantly different.

"Acute heart failure patients are a very diverse group, with complex features based on blood pressure and how well the heart functions (i.e. ejection fraction).  Future studies of AHF should evaluate therapies based on these important but targeted subsets," he said. "There is a need for therapies that can improve kidney function in patients with acute heart failure. However, for now, this therapy continues to remain evasive and continued research is necessary."

Co-authors are Barry A. Borlaug, Kevin J. Anstrom, G. Michael Felker, Michael M. Givertz, Anita Deswal, Bradley A. Bart, Lynne W. Stevenson, Jean L. Rouleau, Eileen O'Meara, Martin M. LeWinter, David A. Bull, Josef Stehlik, Marc J. Semigran, Steven R. Goldsmith, Elizabeth O. Ofili, Christopher M. O'Connor, W.H. Wilson Tang, Randall  C. Starling, Javed Butler, David J. Whellan, Kenneth B. Margulies, Thomas P. Cappola, Marvin A. Konstam, Douglas L. Mann, Victor Davila-Roman, Steven E. McNulty, Eric J. Velazquez, Kerry L. Lee, Monica R. Shah, Adrian F. Hernandez, Eugene Braunwald, Margaret M. Redfield; NHLBI Heart Failure Clinical Research Network.

The National Heart, Lung, and Blood Institute funded the study.