Assessment of anti-ischemic and antianginal effect at trough plasma concentration and safety of trimetazidine MR 35 mg in patients with stable angina pectoris: a multicenter, double-blind, placebo-controlled study.

OBJECTIVE: The study aimed to assess, at trough plasma concentration, the anti-ischemic and antianginal efficacy and tolerability of trimetazidine modified release (MR) 35 mg taken twice daily by patients with stable angina pectoris.

DESIGN: This multicenter, randomized, double-blind, placebo-controlled, international study started with a run-in period of 3 weeks with atenolol 50 mg/day and placebo, followed by a 6-month treatment period with once daily atenolol 50 mg and twice daily trimetazidine MR 35 mg or placebo.

PATIENTS: The study involved 223 patients with stable angina pectoris (class II or III of the Canadian Cardiovascular Society [CCS] classification). 180 patients were analyzed in the full analysis set (FAS) following the intention to treat principle (ITT) and 167 patients were analyzed in the per protocol set (PPS). The PPS data are presented here.

INTERVENTIONS: Two exercise tolerance tests (ETTs) were performed during the run-in period in order to assess the stability of exercise tolerance before angina pectoris and significant ST segment depression. Efficacy was assessed by a third ETT performed after 8 weeks of treatment, at trough, 12 hours after the intake of the drug. Safety was evaluated over the 6-month duration of the study.

MAIN OUTCOMES MEASURES: Time to 1 mm ST segment depression.

RESULTS: Time to 1 mm ST segment depression was increased by 44 seconds more in the trimetazidine MR 35 mg group than in the placebo group (p = 0.005). A significant difference was also evidenced for the time to onset of angina pectoris (p = 0.049) and for the reason for stopping the exercise (p = 0.02). No difference between groups was found for safety parameters.

CONCLUSION: This study demonstrates the anti-ischemic and antianginal efficacy of trimetazidine MR 35 mg twice daily at trough plasma concentrations in patients with stable angina pectoris receiving atenolol 50 mg/day. Furthermore, the drug is well tolerated over 6 months.