Tri-Plus Mechanism of Action

Pharmacotherapeutic group: Other cardiovascular antianginal drug. ATC code: C01EB15 (C: cardiovascular system).
Pharmacology: Pharmacodynamics: Mechanism of action: Trimetazidine inhibits B-oxidation of fatty acids by blocking long-chain 3-ketoacyl-CoA thilase, which enhances glucose oxidation. In an ischaemic cell, energy obtained during glucose oxidation requires less oxygen consumption than in B-oxidation process. Potentiation of glucose oxidation optimizes cellular energy processes, thereby maintaining proper energy metabolism during ischaemia.
Pharmacodynamic effects: In patients with ischaemic heart disease, trimetazidine acts as a metabolic agent, preserving the myocardial high-energy phosphatase intracellular levels. Anti-ischaemic effects are achieved without concomitant haemodynamic effects.
Clinical efficacy and safety: Clinical studies have demonstrated the efficacy and safety of trimetazidine in the treatment of patients with chronic angina, either alone or when the benefit from other antianginal medicinal products was insufficient.
In a 426-patients randomized, double blind, placebo controlled study (Trimpol-II), trimetazidine (60 mg/day) added to metoprolol 100 mg daily (50 mg b.i.d.) for 12 weeks significantly improved statistically exercise tests parameters and clinical symptoms as compared to placebo: total exercise duration +20.1a, p=0.023, total workload +0.54 METs, p=0.001, time to onset of angina +33.9 s, <0.001, angina attacks/week -0.73, p=0.014 and short acting nitrates consumption/week, -0.63, p=0.032, without haemodynamic changes. In a 223 patients randomized, double blind, placebo-controlled study (Sellier), one 35 mg trimetazidine modified release tablet (b.i.d.) added to 50 mg atenolol (o.d.) for 8 weeks produced a significant increase (+34.4 s, p=0.03) in the time to 1-mm ST-segment depression in exercise tests, in a sub-group of patients (n=173), when compared to placebo, 12 hours after taking the drug. A significant difference was also evidenced for the time to onset of angina pectoris (p=0.049). No significant difference between groups could be found for the other secondary endpoints (total exercise duration, total workload and clinical endpoints).
In a 1962 patients three-month randomised, double-blinded study (Vasco study) on top of atenolol 50 mg/day, two dosages of trimetazidine (70 mg/day and 140 mg/day) were tested versus placebo. In the overall population, including both asymptomatic and symptomatic patients, trimetazidine failed to demonstrate a benefit on both ergometric (total exercise duration, time to onset of 1 mm ST and time to onset angina) and clinical endpoints. However, in the subgroup of symptomatic patients (n=1574) defined in a post-hoc analysis, trimetazidine (140 mg) significantly improved total exercise duration (+23.8 s versus +13.1 s placebo; p=0.001) and time onset of angina (+46.3 s versus +32.5 s placebo; p=0.005).
Pharmacokinetics: It is well absorbed and metabolised in the liver to inactive metabolites, then excreted in urine with a T% of 5-6 hours.