Impact of point-of-care testing for CYP2C19 on platelet inhibition in patients with acute coronary syndrome and early dual antiplatelet therapy in the emergency setting

Thromb Res. 2014 Jul;134(1):105-10. doi: 10.1016/j.thromres.2014.05.006. Epub 2014 May 10.

Abstract

Aims: Only limited data exist about the role of point of care CYP2C19 testing in the acute setting in the early phase of acute coronary syndromes (ACS). Therefore, the present study was designed to investigate the impact of CYP2C19 loss-of-function point-of-care (POC) genotyping in patients presenting with acute coronary syndromes (ACS) and treated with dual antiplatelet therapy in the emergency setting.

Methods and results: 137 subjects with ACS scheduled for percutaneous coronary intervention were consecutively enrolled. Pre- and on-treatment platelet aggregation was assessed by multiple electrode aggregometry (MEA) after stimulation with adenosine diphosphate (ADP). Patients were loaded according to current guideline adherent indications and contraindications for use of P2Y12 inhibitors in ACS. POC genotyping for CYP2C19*2 was performed in the emergency room after obtaining a buccal swab using the Spartan RX CYP2C19 system and obtaining patient's informed consent. Prasugrel and ticagrelor treated patients had significantly lower PR compared to clopidogrel-treated patients. The benefits of prasugrel and ticagrelor compared to clopidogrel treated patients in terms of platelet inhibition were more pronounced in CYP2C19*2 carriers. Non-carriers showed similar inhibition regardless of particular P2Y12 inhibitor treatment. Statistical analyses adjusting for factors associated with response (e.g. smoking) revealed that CYP2C19*2 allele carrier status and loading with different type of P2Y12 receptor blockers were significant predictors of on-treatment platelet reactivity in the early phase of ACS.

Conclusion: The results of this pilot study of treatment of patients in the early phase of ACS indicate that CYP2C19*2 POC genotyping might help to identify patients at risk with poor response to clopidogrel treatment, thereby benefiting from reloading and switching to alternative P2Y12 receptor inhibition.

Keywords: Acute coronary syndrome; CYP2C19; Clopidogrel; Pharmacogenetics; Prasugrel; Ticagrelor.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / enzymology*
  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Adenosine / therapeutic use
  • Aged
  • Aspirin / therapeutic use
  • Cytochrome P-450 CYP2C19 / analysis
  • Cytochrome P-450 CYP2C19 / genetics*
  • Female
  • Humans
  • Male
  • Pilot Projects
  • Piperazines / pharmacology
  • Piperazines / therapeutic use*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Point-of-Care Systems
  • Prasugrel Hydrochloride
  • Thiophenes / pharmacology
  • Thiophenes / therapeutic use*
  • Ticagrelor

Substances

  • Piperazines
  • Platelet Aggregation Inhibitors
  • Thiophenes
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Prasugrel Hydrochloride
  • Ticagrelor
  • Adenosine
  • Aspirin