engleski

CYP2C19*2 genotype influence in acute coronary syndrome patients undergoing serial clopidogrel dose tailoring based on platelet function testing : analysis from randomized controlled trial NCT02096419.

Aspirin and a P2Y12 inhibitor administration are crucial in acute coronary syndrome (ACS) and percutaneous coronary intervention. ADP- induced high on-treatment platelet reactivity (HTPR) increases the rate of adverse ischemic events and whether it is a modifiable risk factor for future events is not clear. CYP2C19 enzyme plays a significant role in clopidogrel bioactivation and its polymorphism can cause clopidogrel pharmacodynamic effect reduction. Earlier, we performed a clopidogrel dose tailoring trial based on serial platelet function testing (PFT) using Multiplate® electrode aggregometry during 12 months to maintain optimal platelet reactivity (PR) in ACS patients presenting with HTPR. Patients were randomly assigned to an interventional group taking up to two additional 600 mg loading doses and a range of 75-300 mg maintenance dose, and a control group on standard clopidogrel maintenance dose. Patients in the interventional group maintained better PR during follow-up and had better outcome. In this exploratory analysis we sought to evaluate the effect of CYP2C19*2 genotype on PR levels in both groups of patients during the initial trial. There were no differences in PR between CYP2C19*2 carriers and non-carriers in the interventional group (p=0.187) while CYP2C19*2 carriers had significantly higher PR compared to non-carriers in the control group (p<0.05). Adjusting clopidogrel dose after PFT to reach and maintain optimal PR might overcome unfavorable genotype in ACS patients initially presenting with HTPR. This implies that strategies of antiplatelet therapy tailoring studies should be focused on maintaining optimal PR phenotype, rather than adjusting P2Y12 inhibition based on genotype to improve outcomes.

acute coronary syndrome; platelet function testing; clopidogrel; pharmacogenetics; CYP2C19; tailoring therapy

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