The effects of adenosine A(1) receptor antagonism in patients with acute decompensated heart failure and worsening renal function: the REACH UP study.
BACKGROUND
Worsening renal function (WRF) portends a poor prognosis, and recent deterioration in creatinine might identify patients with elevated intrarenal adenosine in whom adenosine A(1) antagonism may improve renal hemodynamics and function. The purpose of this pilot study was to assess whether rolofylline, an adenosine A(1) antagonist (A(1)RA), would facilitate diuresis while maintaining renal function in patients with acutely decompensated heart failure (ADHF) and recent WRF.


RESULTS
Seventy-six patients with ADHF, volume overload, and recent renal deterioration received rolofylline (30 mg, n = 36) or placebo (n = 40) for 3 days. Rolofylline did not demonstrate a beneficial effect on the primary end points of worsening heart failure or renal function after admission or death or readmission within 30 days. Similar proportions of patients receiving rolofylline (33%) and placebo (30%) were treatment failures within 30 days. However, persistent renal impairment (through Day 14) tended to be less common with rolofylline (6%) than placebo (18%). At Day 14, 11 patients receiving placebo and 13 patients receiving rolofylline had a decrease in creatinine > or = 0.3 mg/dL. There were fewer heart failure readmissions with rolofylline (n = 2) than with placebo (n = 7) through Day 60.


CONCLUSIONS
The Placebo-Controlled Study of the Effects of KW-3902 Injectable Emulsion on Heart Failure Signs and Symptoms, Diuresis, Renal Function, and Clinical Outcomes in Subjects Hospitalized with Worsening Renal Function and Heart Failure Requiring Intravenous Therapy (ie, REACH UP) study did not demonstrate any clear benefit of rolofylline in patients with ADHF and worsening renal function. However, beneficial trends raise the possibility that A(1)RAs might prevent renal dysfunction in these high risk patients. To test this hypothesis, further larger studies need to evaluate the effects of adenosine A(1) antagonists in patients with progressive renal dysfunction in the face of active heart failure therapy.
Gottlieb
Stephen S
SS
University of Maryland School of Medicine, 22 S. Greene St, Baltimore, MD 21209, USA. sgottlie@medicine.umaryland.edu
Givertz
Michael M
MM
Metra
Marco
M
Gergich
Kevin
K
Bird
Steven
S
Jones-Burton
Charlotte
C
Massie
Barry
B
Cotter
Gad
G
Ponikowski
Piotr
P
Weatherley
Beth
B
O'Connor
Christopher
C
Dittrich
Howard
H
D058916:Adenosine A1 Receptor Antagonists / Q000627:therapeutic use*; D000368:Aged; D016001:Confidence Intervals; D003404:Creatinine / Q000378:metabolism*; D004232:Diuretics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D008297:Male; D016017:Odds Ratio; D010865:Pilot Projects; D011379:Prognosis; D043682:Receptor, Adenosine A1 / Q000187:drug effects*; D006435:Renal Dialysis; D018570:Risk Assessment; D016896:Treatment Outcome; D014481:United States; D014970:Xanthines / Q000627:therapeutic use*
D058916:Adenosine A1 Receptor Antagonists; D004232:Diuretics; D043682:Receptor, Adenosine A1; D014970:Xanthines; C073525:rolofylline; D003404:Creatinine