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CLINICAL STUDIES

Effects of BG9719 (CVT-124), an A₁-Adenosine receptor antagonist, and furosemide on glomerular filtration rate and natriuresis in patients with congestive heart failure

Stephen S. Gottlieb, MD, FACC^*, Sandra L. Skettino, MD, Andrew Wolff, MD, Evan Beckman, MD, Michael L. Fisher, MD, FACC^*, Ronald Freudenberger, MD, FACC^*, Tim Gladwell, PharmD^*, Joanne Marshall, RN^*, Michelle Cines, RN^*, Donald Bennett, PhD and Elizabeth B. Liittschwager, BA

^* Division of Cardiology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA and the D.V.A. Medical Center, Baltimore, Maryland
CV Therapeutics, Palo Alto, California, USA
Biogen, Cambridge, Massachusetts, USA

Manuscript received December 31, 1998; revised manuscript received July 29, 1999, accepted October 5, 1999.

Reprint requests and correspondence: Dr. Stephen S. Gottlieb, Division of Cardiology, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, Maryland 21201
sgottlie{at}medicine.umaryland.edu

OBJECTIVES

To determine the effects of furosemide and the selective A₁ adenosine receptor BG9719 on renal function in patients with congestive heart failure (CHF).

BACKGROUND

Studies suggest that adenosine may affect renal function by various mechanisms, but the effects of blockade of this system in humans is unknown. In addition, the effects of a therapeutic dose of furosemide on glomerular filtration rate (GFR) and renal plasma flow (RPF) in heart failure patients are controversial.

METHODS

On different days, 12 patients received placebo, BG9719 and furosemide. Glomerular filtration rate, RPF and sodium and water excretion were assessed immediately following drug administration.

RESULTS

Glomerular filtration rate was 84 ± 23 ml/min/1.73m² after receiving placebo, 82 ± 24 following BG9719 administration and a decreased (p < 0.005) 63 ± 18 following furosemide. Renal plasma flow was unchanged at 293 ± 124 ml/min/1.73m² on placebo, 334 ± 155 after receiving BG9719 and 374 ± 231 after receiving furosemide. Sodium excretion increased from 8 ± 8 mEq following placebo administration to 37 ± 26 mEq following BG9719 administration. In the six patients in whom it was measured, sodium excretion was 104 ± 78 mEq following furosemide administration.

CONCLUSIONS

Natriuresis is effectively induced by both furosemide and the adenosine A₁ antagonist BG9719 in patients with CHF. Doses of the two drugs used in this study did not cause equivalent sodium and water excretion but only furosemide decreased GFR. These data suggest that adenosine is an important determinant of renal function in patients with heart failure.

Abbreviations and Acronyms   CHF = congestive heart failure   GFR = glomerular filtration rate   RPF = renal plasma flow

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