Safety, tolerability, and antiischaemic efficacy of ITF-296, a nitric oxide donor, in patients with chronic stable angina.
A double-blind, placebo-controlled, parallel-group, dose-escalation study was performed to evaluate ITF-296, a new nitric oxide donor, in chronic stable angina. Twenty-four male patients underwent exercise electrocardiography in conjunction with echocardiography on three separate occasions within 2 weeks. After two reproducibility tests, the third exercise test was immediately preceded by a 30-min intravenous infusion of either placebo or 0.3, 1.0, or 3.0 microg/kg/min of ITF-296, with six patients in each treatment group. During ITF-296 infusion, systolic blood pressure decreased by a mean of 12 mm Hg compared with a 2 mm Hg increase in the placebo group [difference, -14; 95% confidence interval (CI), -23 to -6 mm Hg]. ITF-296 administration was followed by consistent increases in total exercise time, time to angina threshold, and time to 1-mm ST-segment depression. The mean change in total exercise time was 39 s on placebo and 94 s on ITF-296 (mean difference, 54 s; 95% CI, -48 to 157 mm Hg). The 1.0- and 3.0-microg/kg/min doses increased exercise time by >2 min with no important change in peak rate-pressure product compared with baseline. The trends exhibited in this small preliminary study were consistently pharmacologically plausible and indicate that ITF-296 shows potential antiischaemic efficacy in patients with chronic stable angina.
Khattar
R S
RS
Department of Cardiac Research, Northwick Park Hospital, Harrow, England, UK.
Senior
R
R
Sardina
M
M
Boyce
M
M
Lahiri
A
A
D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy*; D048588:Benzoxazines; D004311:Double-Blind Method; D005080:Exercise Test; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000517:prevention & control*; D009566:Nitrates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010078:Oxazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D048588:Benzoxazines; D009566:Nitrates; D010078:Oxazines; C091726:sinitrodil