title: The new oral adenosine A1 receptor agonist capadenoson in male patients with stable angina.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Third Division of Cardiology, Medical University of Silesia, Katowice, Poland. michal.tendera@gcm.pl
authors.forename: Michal
authors.initials: M
authors.lastname: Tendera
authors.forename: Ewa
authors.initials: E
authors.lastname: Gaszewska-Żurek
authors.forename: Zofia
authors.initials: Z
authors.lastname: Parma
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.forename: Ewa
authors.initials: E
authors.lastname: Jankowska
authors.forename: Kalina
authors.initials: K
authors.lastname: Kawecka-Jaszcz
authors.forename: Danuta
authors.initials: D
authors.lastname: Czarnecka
authors.forename: Maria
authors.initials: M
authors.lastname: Krzemińska-Pakuła
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Bednarkiewicz
authors.forename: Maciej
authors.initials: M
authors.lastname: Sosnowski
authors.forename: Michael
authors.initials: M
authors.lastname: Ochan Kilama
authors.forename: Rahul
authors.initials: R
authors.lastname: Agrawal
mesh_terms: D058907:Adenosine A1 Receptor Agonists / Q000008:administration & dosage*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000631:Aminopyridines / Q000008:administration & dosage*; D000704:Analysis of Variance; D060050:Angina, Stable / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011044:Poland; D043682:Receptor, Adenosine A1 / Q000187:drug effects* / Q000378:metabolism; D012737:Sex Factors; D013844:Thiazoles / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058907:Adenosine A1 Receptor Agonists; D000631:Aminopyridines; D043682:Receptor, Adenosine A1; D013844:Thiazoles; C575871:capadenoson