TRimetazidine as an Agent to affeCt clopidogrEl Response: The TRACER Study

INTRODUCTION: This prospective study aimed to determine whether trimetazidine (TMZ) alters the pharmacodynamic (PD) effects of clopidogrel. METHODS: Patients with stable coronary artery disease (SCAD) (n = 24) who were actively treated with dual antiplatelet therapy (DAPT) of aspirin 81 mg daily and clopidogrel 75 mg daily were recruited. Platelet function was measured with the VerifyNow P2Y12 assay (Accriva Diagnostics, San Diego, CA, USA) and assessed before the initiation of and after 14 days of treatment with TMZ. Results were compared using a paired t test. RESULTS: Almost 80% of the study population were of South Asian descent and had diabetes mellitus (DM). P2Y12 reaction units (PRUs) were higher in patients on TMZ (204 ± 56 compared with 174 ± 71 before TMZ, p = 0.005). The average increase in PRU score was 29 (95% confidence interval 8.8–49.7). Before TMZ, the proportion of patients with high on-treatment platelet reactivity (PRU > 208 units) was 25%, which increased to 42% for patients on TMZ. CONCLUSION: Higher platelet reactivity was seen in patients on TMZ, suggesting that TMZ attenuated the PD effects of clopidogrel in this study of a predominantly South Asian diabetic subpopulation. Alternative therapies should be considered and further research is warranted. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03603249.