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Haemodynamic effects of rolofylline in the treatment of patients with heart failure and impaired renal function
Author(s) -
Ponikowski Piotr,
Mitrovic Veselin,
O'Connor Christopher M.,
Dittrich Howard,
Cotter Gad,
Massie Barry M.,
Givertz Michael M.,
Chen Erluo,
Murray Meredith,
Weatherley Beth D.,
Fujita Kenji P.,
Metra Marco
Publication year - 2010
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1093/eurjhf/hfq137
Subject(s) - medicine , heart failure , impaired renal function , cardiology , hemodynamics , renal function
Aims The direct effects of adenosine A1 receptor antagonists on haemodynamic parameters in patients with acute heart failure (HF) remain largely unknown. Methods and results We evaluated the haemodynamic effects of the AA 1 RA rolofylline in 59 HF patients with concomitant renal impairment (estimated creatinine clearance 20–80 mL/min). Placebo or rolofylline 30 mg was administered as a 4 h infusion followed by intravenous (i.v.) loop diuretic administration. Haemodynamic measurements were carried out hourly up to 8 h post‐dosing by pulmonary artery catheterization. Urine output, fractional excretion of sodium, potassium, urea, and uric acid, and blood urea nitrogen (BUN) and creatinine levels were also measured. In both groups, the changes from baseline in all haemodynamic indices except mean pulmonary artery pressure (PAP) were not clinically significant. Mean [95% confidence interval (CI)] PAP showed a placebo‐adjusted decrease with rolofylline of −1.5 (−4.1, 1.1)mmHg at Hour 4 and −3.5 mmHg (95% CI: −6.2, −0.2) at Hour 8. There was a significant increase with rolofylline in diuresis [placebo‐corrected mean (95% CI) change of 68 (20, 116)mL/h at Hour 2–4 and 103 (21, 185)mL/h at Hour 4–8] and in fractional excretion of sodium, potassium, and uric acid. Placebo‐corrected changes in plasma levels of creatinine and BUN with rolofylline were non‐significant. Conclusion Single administration of rolofylline in patients with HF and impaired renal function produced a slight decrease in mean PAP and consistently increased diuresis and natriuresis without compromising renal function, both before and after administration of i.v. loop diuretics.