Adenosine1 receptor antagonism: a new therapeutic approach for the treatment of decompensated heart failure.
Heart failure (HF) remains a major cause of morbidity and mortality, even with the use of standard treatments in patients with chronic HF and acute decompensated HF. Impaired renal function is an important prognostic indicator for adverse clinical outcomes. Elevated plasma levels of adenosine have been observed in HF patients and stimulation of adenosine1 receptors (A1R) in the kidney may be contributing to impaired renal function and treatment resistance. This observation has led to the development of A1R inhibitor drugs, both in oral and intravenous formulations, which in both animal and preliminary clinical trials have been shown to augment diuresis while preserving or improving renal function in HF patients. An extensive phase III clinical program using the A1R KW-3902 is now in progress in patients with symptomatic HF and renal dysfunction to evaluate the efficacy and safety of this treatment approach.
Shah
Rena H
RH
Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla, New York 10595, USA.
Frishman
William H
WH
D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D004195:Disease Models, Animal; D004232:Diuretics / Q000627:therapeutic use; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology; D014970:Xanthines / Q000627:therapeutic use
D058916:Adenosine A1 Receptor Antagonists; D004232:Diuretics; D014970:Xanthines; C073525:rolofylline