The Clinical Implementation of CYP2C19 Genotyping in Patients with an Acute Coronary Syndrome: Insights From the FORCE-ACS Registry

J Cardiovasc Pharmacol Ther. 2023 Jan-Dec:28:10742484231210704. doi: 10.1177/10742484231210704.

Abstract

Background: Guidelines recommend prasugrel or ticagrelor for acute coronary syndrome (ACS) patients. However, these P2Y12 inhibitors increase bleeding risk compared to clopidogrel. Although genotype-guided P2Y12-inhibitor selection has been shown to reduce bleeding risk, data on its clinical implementation is lacking.

Methods: The study included ACS patients receiving genotype-guided antiplatelet therapy, utilising either a point-of-care (POC) device or laboratory-based testing. We aimed to collect qualitative and quantitative data on genotyping, eligibility for de-escalation, physician adherence to genotype results, time to de-escalation and cost reduction.

Results: Of the 1,530 patients included in the ACS registry from 2021 to 2023, 738 ACS patients treated with ticagrelor received a CYP2C19 genotype test. The median turnover time of genotyping was 6.3 hours (interquartile range [IQR], 3.2-16.7), with 82.3% of the genotyping results known within 24 hours after admission. POC genotyping exhibited significantly shorter turnaround times compared to laboratory-based testing (with respective medians of 5.7 vs 47.8 hours; P < .001). Of the genotyped patients, 81.7% were eligible for de-escalation which was carried out within 24 hours in 70.9% and within 48 h in 93.0%. The time to de-escalation was significantly shorter using POC (25.4 hours) compared to laboratory-based testing (58.9 hours; P < .001). Implementing this strategy led to a reduction of €211,150.50 in medication costs.

Conclusions: CYP2C19 genotype-guided-de-escalation in an all-comers ACS population is feasible. POC genotyping leads to shorter turnaround times and quicker de-escalation. Time to de-escalation from ticagrelor to clopidogrel in noncarriers was short, with high physician adherence to genotype results.

Keywords: CYP2C19 genotyping; acute coronary syndrome; de-escalation strategy; rapid point-of-care genotyping.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome* / diagnosis
  • Acute Coronary Syndrome* / drug therapy
  • Acute Coronary Syndrome* / genetics
  • Clopidogrel / adverse effects
  • Cytochrome P-450 CYP2C19 / genetics
  • Genotype
  • Humans
  • Percutaneous Coronary Intervention* / adverse effects
  • Platelet Aggregation Inhibitors / adverse effects
  • Prasugrel Hydrochloride / therapeutic use
  • Ticagrelor / adverse effects
  • Treatment Outcome

Substances

  • Clopidogrel
  • Platelet Aggregation Inhibitors
  • Ticagrelor
  • Cytochrome P-450 CYP2C19
  • Prasugrel Hydrochloride
  • CYP2C19 protein, human