Effects of the Adenosine A1 Receptor Antagonist Rolofylline on Renal Function in Patients With Acute Heart Failure and Renal Dysfunction: Results From PROTECT (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function)

Study Questions:

What are the effects of rolofylline on renal function in patients with acute heart failure (AHF) and renal dysfunction randomized in the PROTECT study?


The study cohort was comprised of 2,033 patients with AHF, volume overload, estimated creatinine clearance between 20 and 80 ml/min, and elevated natriuretic peptide levels. They were randomized (2:1) within 24 hours of hospital presentation to rolofylline 30 mg/day or intravenous placebo for up to 3 days. Creatinine was measured daily until discharge or day 7 and on day 14. Persistent worsening renal function was defined as an increase in serum creatinine >0.3 mg/dl at both days 7 and 14, or initiation of hemofiltration or dialysis or death by day 7.


The investigators found that at baseline, mean ± standard deviation estimated creatinine clearance was 51.0 ± 20.5 ml/min in the placebo group and 50.4 ± 20.0 ml/min in the rolofylline group. Similar changes in creatinine and estimated creatinine clearance between placebo- and rolofylline-treated patients during hospitalization and at day 14 was observed. Mean body weight was reduced by 2.6 and 3.0 kg in placebo and rolofylline patients, respectively (p = 0.005) after 4 days. They found persistent worsening renal function in 13.7% of the placebo group and 15.0% of the rolofylline group (odds ratio vs. placebo, 1.11; 95% confidence interval, 0.85-1.46; p = 0.44).


The authors concluded that adenosine A1 receptor antagonist rolofylline did not prevent persistent worsening renal function in AHF patients with volume overload and renal dysfunction.


The Consensus Conference on Cardio-Renal Syndromes identified five subtypes that have different pathophysiology (refer to Figures 1-5 in J Am Coll Cardiol 2008;52:1527-39), prevention, and management strategies (refer to Table 1 in a recent article). Further studies are needed to determine whether adenosine A1 receptor antagonist rolofylline is indeed effective in one of the subtypes of cardiorenal syndromes before abandoning this very promising therapeutic agent.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Chronic Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Renal Dialysis, Hemofiltration, Kidney Function Tests, Biological Markers, Cardio-Renal Syndrome, Body Weight, Xanthines, Creatinine, Receptor, Adenosine A1, Hospitalization

< Back to Listings