Abstract

Objective To assess antianginal efficacy and possible adverse haemodynamic effects of combination treatment with trimetazidine and diltiazem in patients with stable angina.

Design Double blind, randomised, placebo controlled trial of four weeks duration.

Setting Outpatient department of two Indian hospitals.

Subjects 64 male patients with stable angina, uncontrolled on diltiazem alone.

Interventions Diltiazem 180 mg and trimetazidine 60 mg, or diltiazem 180 mg and placebo daily.

Main outcome measure Change in exercise time to 1 mm ST segment depression.

Results 33 patients (55%) had no exercise induced angina at 3 mm ST segment depression at inclusion in the study (silent ischaemia). Intention to treat analysis showed that of 32 patients in each treatment group, the number (%) of patients responding to trimetazidine compared to placebo was: for anginal attacks, 28 (87.5)v 15 (46.9), p < 0.001; for exercise time to 1 mm ST segment depression, 21 (65.6) v 9 (28.1), p < 0.003; for exercise time to angina, 12 (37.5) v 5 (15.6), p < 0.05; and for maximum work at peak exercise, 17 (53.1)v 8 (25), p < 0.02. Compared to placebo, there was net improvement with trimetazidine in mean anginal attacks of 4.8/week (95% confidence interval (CI) 7.5 to 2.1; p < 0.002); in mean exercise times at 1 mm ST segment depression of 94.2 seconds (95% CI 182.8 to 5.6; p < 0.05), and at onset of angina of 113.1 seconds (95% CI 181.6 to 44.6; p < 0.02); and in mean maximum work at peak exercise of 1.4 metabolic equivalents (95% CI 2.4 to 0.3; p < 0.05).

Conclusions Patients with stable angina uncontrolled with diltiazem had a clinically important improvement after combination treatment with trimetazidine, without adverse haemodynamic events or increased side effects.