Safety and Tolerability of Neladenoson Bialanate, a Novel Oral Partial Adenosine A1 Receptor Agonist, in Patients With Chronic Heart Failure.
We studied safety and tolerability of neladenoson bialanate, a novel oral selective partial adenosine A1 receptor agonist that maintains the cardioprotective effects of adenosine without the undesired side effects of a full agonist, in 2 pilot studies in patients with heart failure with reduced ejection fraction (HFrEF). The β-blocker interaction study was a single-blind, placebo-controlled study on the effects of a 30-mg single dose of neladenoson bialanate on atrioventricular (AV) conduction in 11 patients with HFrEF treated with β-blockers. The PARSiFAL pilot study was a double-blind, placebo-controlled study on the effects of a 7-day treatment with 10 or 20 mg neladenoson bialanate or placebo in 31 patients with HFrEF on β-blocker therapy. In the β-blocker interaction study with 11 HFrEF patients, no second- or third-degree AV block was detected on 48-hour Holter monitoring. In the 31 HFrEF patients included in the PARSiFAL pilot study, no second- or third-degree AV blocks were observed during 24-hour Holter monitoring, and no effects were seen on heart rate and blood pressure. Median absolute changes in LVEF, measured by cardiac magnetic resonance, were 1.9% (interquartile range -1.1 to 4.3), 0.3% (-1.4 to 2.7), and 2.2% (0.4 to 4.5), in the placebo, 10-mg, and 20-mg groups, respectively. Treatment of HFrEF patients with the novel partial adenosine A1 agonist neladenoson bialanate appeared to be safe in 2 small pilot studies, and no atrioventricular conduction disorders or neurological side effects were observed. No significant early changes in cardiac function were detected.
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Adriaan Alexander
AA
Voors
Department of Cardiology, Campus Virchow, Charite Universitätsmedizin Berlin, Berlin, Germany.
Hans-Dirk
HD
Düngen
Cardiovascular Department, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
Michele
M
Senni
Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University and Civil Hospital of Brescia, Brescia, Italy.
Savina
S
Nodari
Centro Cardiologico Monzino, Milan, Italy.
Piergiuseppe
P
Agostoni
Wroclaw Medical University, Wroclaw, Poland.
Piotr
P
Ponikowski
Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
Jeroen J
JJ
Bax
Division of Cardiology, Stony Brook University, Stony Brook, NY, USA.
Javed
J
Butler
Duke Cardiovascular Magnetic Resonance Center, Duke University Medical Center, Durham, NC, USA.
Raymond J
RJ
Kim
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Bernard
B
Dorhout
Department of Cardiology, Witten, Germany; Drug Discovery, Clinical Sciences, Bayer Pharma AG, Witten University, Wuppertal, Germany.
Wilfried
W
Dinh
Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Mihai
M
Gheorghiade
D058907:Adenosine A1 Receptor Agonists / Q000008:administration & dosage*; D000284:Administration, Oral; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D004311:Double-Blind Method; D054333:Drug Partial Agonism; D004562:Electrocardiography / Q000187:drug effects / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology; D006333:Heart Failure / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016037:Single-Blind Method
D058907:Adenosine A1 Receptor Agonists
AV block; cardioprotection; heart failure; neladenoson bialanate; partial adenosine A1 receptor agonist