Abstract 2164: Effect of the Adenosine A1 Receptor Antagonist, KW-3902, on Diuresis and Renal Function in Patients with Acute Decompensated Heart Failure Refractory to Maximum Doses of Conventional Diuretics: A Randomized, Double-Blind, Placebo Controlled, Dose Escalation Study
Background: Some patients with acute decompensated heart failure (ADHF) reach a point where high doses of diuretics are ineffective and may worsen renal function. This refractory state may involve tubuloglomerular feedback (TGF), an adenosine A1 receptor-mediated effect that causes decreased renal blood flow and glomerular filtration rate. KW-3902, an adenosine A1 receptor antagonist, which blocks TGF and has proximal diuretic effects, may therefore be beneficial in increasing urine output without further worsening renal function in ADHF.
Methods: At 11 US sites, 34 patients with ADHF refractory to diuretics received placebo, 10, 30 or 60 mg of KW-3902 IV once over 2 hours. LVEF was not an entry criterion. The study was not powered for statistical significance. Changes from baseline in urine output measured hourly and creatinine clearance (Ccr) measured every 3 hr were the primary and secondary endpoints, respectively.
Results: 33 patients (mean age 66, 44% female) had accurately collected urine samples (baseline Ccr 34.7 mL/min). All doses of KW-3902 increased hourly urine volume compared to placebo with the greatest increase taking place between hours 1–3 in the 30 mg group (Figure⇓). 30 mg of KW-3902 also increased Ccr compared to baseline over 3–9 hours after start of drug infusion (p<0.05). There was either no change or a decrease in Ccr in the placebo group.
Conclusions: These initial results suggest that the adenosine receptor antagonist, KW-3902, may prove beneficial in facilitating diuresis in ADHF patients refractory to conventional pharmacological therapy while simultaneously potentiating renal function. These data need to be confirmed in an adequately powered study.