A dose-dependent improvement in exercise tolerance in patients with stable angina treated with mildronate: a clinical trial "MILSS I".

ABSTRACT

OBJECTIVE: To assess the efficacy of various doses of Mildronate in combination with standard therapy for the exercise tolerance of patients with stable angina pectoris. The primary efficacy variable was the change in exercise time in bicycle ergometry from the baseline to 12 weeks of treatment. The secondary endpoints were the changes in maximum achieved load and time to the onset of angina from the baseline to week 12. MATERIAL AND METHODS: A total of 512 patients with chronic coronary heart disease who had ischemia as the limiting factor in the exercise test from 72 study centers in 4 countries were enrolled in this prospective, randomized, double-blind, placebo controlled phase 2 study. The patients were assigned to either 4 groups receiving standard therapy plus Mildronate at different daily doses or 1 group receiving standard therapy plus placebo. RESULTS: The mean change in the total exercise time in the mildronate 100 mg and mildronate 300 mg groups was -2.12±108.45 and 11.48±62.03 seconds, respectively. The mean change for the placebo group was -7.10±81.78 seconds. The difference between Mildronate 100 mg and 300 mg and placebo groups was not significant. Patients in the Mildronate 1000 mg group showed a remarkable increase in the mean change in the total exercise time (35.18±53.29 seconds, P=0.002). Mildronate at a dose of 3000 mg caused a smaller increase as compared with a dose of 1000 mg. Similar changes in the secondary end parameters were observed. CONCLUSION: The most effective dose of Mildronate in combination with standard therapy was found to be 500 mg twice a day.