The new oral adenosine A1 receptor agonist capadenoson in male patients with stable angina
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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.
KeywordsCoronary artery disease Stable angina Capadenoson A1 receptor agonists Heart rate Exercise testing
The study was funded by Bayer Schering Pharma, Wuppertal, Germany.
- 8.Fox K, Ford I, Steg PG, Tendera M, Robertson M, BEAUTIFUL investigators (2008) Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet 372:817–821PubMedCrossRefGoogle Scholar
- 13.Auchampack JA, Gross GJ (1993) Adenosine A1 receptors, KATP channels and ischaemic preconditioning in dogs. Am J Physiol 264:H1327–H1336Google Scholar
- 15.Frey R, Mueck W, Delesen H (2006) Single dose, basic phase I dose-escalation study in a randomized, single-blind, placebo-controlled, group comparison design to investigate safety and tolerability of BAY 68-4986 and its pharmacodynamics and pharmacokinetics after oral dosing in 8 healthy male subjects per dose step. Internal Archive, Report Number PH-34381Google Scholar