Rolofylline, an Adenosine A1−Receptor Antagonist, in Acute Heart Failure

• Published in: The New England journal of medicine Vol. 363; no. 15; pp. 1419 - 1428
• Main Authors: Massie, Barry M, O'Connor, Christopher M, Metra, Marco, Ponikowski, Piotr, Teerlink, John R, Cotter, Gad, Weatherley, Beth Davison, Cleland, John G.F, Givertz, Michael M, Voors, Adriaan, DeLucca, Paul, Mansoor, George A, Salerno, Christina M, Bloomfield, Daniel M, Dittrich, Howard C
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 07.10.2010
• Subjects: Acute Disease; Adenosine A1 Receptor Antagonists; adverse effects; Aged; Biological and medical sciences; Cardiology. Vascular system; Dermatologi och venereologi; Dermatology and Venereal Diseases; Diuretics; Diuretics - adverse effects; Diuretics - therapeutic use; Double-Blind Method; Drug dosages; drug therapy; Female; General aspects; Heart; Heart Failure; Heart Failure - drug therapy; Heart Failure - mortality; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Hospitalization; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Kidneys; Male; Medical sciences; Mortality; Odds Ratio; Patient Readmission; Proportional Hazards Models; Risk; Rodents; therapeutic use; Treatment Failure; Xanthines; Xanthines - adverse effects; Xanthines - therapeutic use; Heart failure; Medicine; Heart disease; Acute; Cardiovascular disease; Antagonist; Adenosine receptor
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa0912613

Acute heart failure is a serious disorder often associated with progressive renal dysfunction. In this clinical trial, rolofylline, an adenosine A1–receptor antagonist, did not appear to benefit patients with acute heart failure and renal dysfunction. Preexisting chronic kidney disease and worsening renal function are common in patients hospitalized with acute heart failure and are associated with poor outcomes. 1 – 5 Multiple factors are responsible for this association, 3 – 5 including coexisting conditions, less use of effective therapies in patients with renal dysfunction than in patients without renal dysfunction, and inadequate treatment of volume overload because of a suboptimal response to diuretics or concern regarding diuretic toxicity. 4 , 5 Adenosine has been implicated as an important intrarenal mediator of both worsening renal function and diuretic resistance. 6 , 7 ATP hydrolysis releases free adenosine into the extracellular space, which in turn . . .