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 mu g/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 91 s on ITF-296 (mean difference, 54 s; 95% CI, -48 to 157 mm Hg). The 1.0- and 3.0-mu g/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.