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

Area of Science:

• Pharmacology and Cardiovascular Medicine

Background:

• Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is standard for stable coronary artery disease (SCAD).
• Trimetazidine (TMZ) is used for angina, but its interaction with clopidogrel's pharmacodynamics is not well-established.
• A significant portion of the study population (80%) were of South Asian descent with diabetes mellitus (DM).

Purpose of the Study:

• To investigate whether trimetazidine (TMZ) impacts the pharmacodynamic (PD) effects of clopidogrel in patients with SCAD.
• To assess changes in platelet function in patients receiving both clopidogrel and TMZ.

Main Methods:

• A prospective study involving 24 patients with SCAD on daily aspirin and clopidogrel.
• Platelet function was measured using the VerifyNow P2Y12 assay before and after 14 days of TMZ treatment.
• Paired t-test was used for statistical comparison of results.

Main Results:

• Patients on TMZ showed significantly higher P2Y12 reaction units (PRUs) (204 ± 56) compared to baseline (174 ± 71; p=0.005).
• The average increase in PRU score was 29 units, indicating reduced clopidogrel efficacy.
• The proportion of patients with high on-treatment platelet reactivity (PRU > 208) increased from 25% to 42% with TMZ use.

Conclusions:

• Trimetazidine (TMZ) attenuated the pharmacodynamic effects of clopidogrel, leading to higher platelet reactivity.
• This interaction is particularly relevant in diabetic patients of South Asian descent, a subpopulation with potentially altered drug metabolism.
• Consideration of alternative antiplatelet strategies is recommended, and further research is warranted to confirm these findings.