Effect of acadesine, a new metabolic agent, on exercise-induced myocardial ischemia in chronic stable angina.
Acadesine, the first of a class of adenosine-regulating agents, has been shown to possess antiischemic properties in animal models. The aim of the study was to assess the effect of acadesine on exercise-induced myocardial ischemia in patients with chronic stable angina pectoris. Twelve patients with stable angina entered a five-way, randomized double-blind study comparing the effects of four doses of acadesine with placebo on time to 1 mm ST-segment depression and other parameters of exercise tolerance. At each study period patients underwent baseline exercise testing, followed by drug or placebo infusion after a 60 minute rest period. The exercise test was repeated after 30 minutes infusion, which continued throughout recovery. Time to angina, time to 1 mm ST depression, and total exercise time during the placebo infusion were 301.1 +/- 45.3, 314.8 +/- 50.9, and 399.4 +/- 47.6 seconds. The placebo-adjusted percentage change in time to 1-mm ST segment with acadesine 6, 12, 24, and 48 mg/kg was -0.1 +/- 6.2%, 11.1 +/- 13.8%, 12.9 +/- 8.6%, and -3.2 +/- 6.8%, respectively (p = NS vs. baseline). Time to angina, total exercise time, and recovery time of the ST segment were not consistently altered by acadesine. The lack of effect across all acadesine doses is consistent with animal data from ischemia-reperfusion injury studies, where a clear dose dependency was present with a loss of effect at higher doses. Alternatively, the extent of ischemia induced by treadmill exercise may have been insufficient for the antiischemic activity of acadesine to be evident.
Holdright
D R
DR
Royal Brompton National Heart and Lung Hospital, London, UK.
Sparrow
J L
JL
Wright
C L
CL
Steiner
J
J
Fox
K M
KM
D000368:Aged; D000620:Aminoimidazole Carboxamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000787:Angina Pectoris / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005080:Exercise Test / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000209:etiology*; D010919:Placebos; D012263:Ribonucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
D010919:Placebos; D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C011651:acadesine