The new oral adenosine A1 receptor agonist capadenoson in male patients with stable angina

Anti-ischaemic effect of A1 adenosine receptor agonists was shown in animal and preclinical studies. The present proof-of-concept study aimed at evaluation of the efficacy and safety of a new adenosine A1 receptor agonist capadenoson in patients with stable angina. This was a randomized, double-blind, placebo-controlled, single dose-escalating, multicenter trial comparing the effect of capadenoson at 1, 2.5, 5, 10, and 20 mg versus placebo. For each dose step patients were randomized to receive single doses of either capadenoson or matching placebo in a 5:1 ratio. The primary efficacy variable was the absolute difference in heart rate (HR) at maximum comparable level of workload between baseline and post dose exercise tolerance test at maximum concentration of capadenoson. Capadenoson effect on total exercise time and time to 1-mm ST-segment depression were also measured. Sixty-two male patients with stable angina were enrolled in the study. There was a consistent trend for HR reduction at comparable maximum work load in active treatment groups, with significant differences against placebo for 10 and 20 mg (HR reduction by 12.2 and 6.8 beats per min, p = 0.0002 and p = 0.032, respectively). A statistically significant trend (p = 0.0003) for a reduction in HR with increasing doses of capadenoson was shown. Increases in total exercise time and time to 1-mm ST-segment depression were also observed. In patients with stable angina capadenoson lowers exercise HR at comparable maximum workload, which is associated with improved total exercise time and prolongation of time to ischaemia.