Ambulatory monitoring and exercise testing in the evaluation of a new long-acting calcium ion antagonist KB-944 (Fostedil) for the treatment of exertional angina pectoris

Abstract

The anti-anginal effects of KB-944 (Fostedil), a new calcium ion antagonist with a half life of approximately 23–28 hr, were evaluated in 20 patients with exertional angina pectoris in a placebo-controlled single-blind dose titration trial. Ambulatory monitoring and multistage treadmill exercise with computer-assisted electrocardiographic analysis was performed after 2 weeks of placebo therapy and after two 2-weekly periods of KB-944 therapy. The mean (±SEM) exercise time to the development of angina on treadmill walking increased from 6.9 ± 0.4 min on placebo to 9.4 ± 0.5 min on KB-944 100 mg/day ( P < 0.001) and 9.7 ± 0.8 min on KB-944 200 mg/day ( P < 0.001 vs placebo and not significant vs KB-944 100 mg/day). The time to the development of 1 mm ST-segment depression of 5.3 ± 0.4 min on placebo increased to 6.5 ± 0.5 and 6.6 ± 0.5 min on KB-944 100 and 200 mg/day, respectively ( P < 0.01 vs placebo). The heart rate at rest of 77 ± 3 beats/min on placebo was reduced to 68 ± 3 beats/min on KB-944 100 mg/day ( P < 0.001) and 71 ± 2 beats/min on KB-944 200 mg/day ( P < 0.01). The maximal heart rate and the rate—pressure product were not altered by KB-944 therapy. One patient developed unstable angina during the treatment phase of KB-944 200 mg/day and was withdrawn. Five patients complained of dyspepsia and one of headache and lethargy during KB-944 200 mg/day. One patient developed ventricular tachycardia during treadmill testing while on KB-944 200 mg/day. The 24-hr ambulatory monitoring data confirmed the findings of exercise testing. KB-944 (Fostedil) in a dose of 100 mg once daily was well tolerated as compared to KB-944 200 mg once daily and both the doses were equally effective. The drug merits further evaluation for the treatment of exertional angina pectoris.