Evaluation of On-Clopidogrel platelet reactivity overtime, SYNTAX SCORE, genetic polymorphisms and their relationship to one year clinical outcomes in STEMI patients undergoing PCI.

Abstract

The aim of this paper was to investigate the variability of On-clopidogrel platelet reactivity overtime, the association between HTPR, gene polymorphism and Syntax Score (SS) for risk prediction of MACE in patients with ST-Elevation Myocardial Infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Platelet function testing may be used to optimize antiplatelet therapy in high-risk patients, but identification of this subset of patients remains a challenge. High on-treatment platelet reactivity (HTPR) has emerged as a risk factor for major adverse cardiovascular events (MACE). Genetic polymorphisms play key role in clopidogrel hypo-responsiveness. This prospective, observational study includes 151 consecutive STEMI patients who underwent PCI and treated with clopidogrel. Platelet Activity Index (PAI) was measured at two different time points post-PCI. Patients were stratified by the presence of HTPR (PAI≥5) and by upper SS (SS≥15). Allele-specific polymerase chain reaction for identifying CYP2C19*2, CYP3A5*3, PON1, P2Y12 gene polymorphisms was done. The end point at one year follow up was MACE. There was a significant increase in mean platelet reactivity and the total number of non-responders over a period of three months (9.9% vs. 23.8% P=0.05). Patients with SS≥15 in the presence of HTPR during follow-up had highest rates of MACE, especially among diabetics compared to non-diabetics (P=0.024). The prevalence of CYP2C19*2 polymorphism was 49%%, was associated with HTPR during follow-up but unassociated with MACE. In STEMI patients undergoing PCI, the presence of SS≥15, HTPR during follow-up were associated with high MACE rates especially among diabetics. Hence, such high-risk groups shall require sequential testing for HTPR and optimize therapy accordingly.