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.