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

Minerva Cardioangiol. 2018 Feb;66(1):16-25. doi: 10.23736/S0026-4725.17.04438-3. Epub 2017 Jul 27.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Adult
  • Aged
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Clopidogrel
  • Cytochrome P-450 CYP2C19 / genetics
  • Diabetes Mellitus / epidemiology
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention / methods*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Function Tests
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Prospective Studies
  • Risk Factors
  • ST Elevation Myocardial Infarction / therapy*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Time Factors

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine