Clinical features of an anti-anginal drug in angina pectoris

Trimetazidine (TMZ) exerts anti-ischaemic effects without any associated central haemodynamic change, both at rest and with exercise. These findings suggest that TMZ has a direct cytoprotective effect, the efficacy of which has been confirmed by clinical studies in effort angina. TMZ as monotherapy when compared with placebo, in acute (60 mg) as well as in chronic (20 mg t.i.d.) administration, significantly improves exercise tolerance: total work, duration of exercise and time to 1 mm ST segment depression, without changing the rate-pressure product. Moreover, during chronic treatment TMZ decreases the rate of anginal attacks. In patients with coronary heart disease insufficiently controlled with nifedipine or a beta-blocker as monotherapy, the addition of TMZ (20 mg t.i.d.) significantly reduces the number of anginal attacks and improves exercise capacity. TMZ antianginal activity in monotherapy has also been compared in double-blind controlled studies with that of a calcium channel antagonist and a beta-blocker as reference drugs. TMZ is as efficient as nifedipine or propranolol on clinical variables as well as on ergometric criteria, but unlike these two reference drugs, which act through a haemodynamic mechanism, TMZ does not decrease rate-pressure product. Furthermore, in the study comparing TMZ with propranolol, TMZ was shown to decrease ischaemic episodes recorded by ECG ambulatory monitoring. These data show that TMZ belongs to the major antianginal agents available today. However, the absence of central haemodynamic effects suggests that the drug has a novel anti-ischaemic mechanism involving direct myocardial cytoprotection.