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The Clinical Implementation of CYP2C19 Genotyping in Patients with an Acute Coronary Syndrome: Insights From the
Jaouad Azzahhafi1, Wout W A van den Broek1, Dean R P P Chan Pin Yin1
1Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands.
Insights
Genotype-guided P2Y12 inhibitor selection in acute coronary syndrome (ACS) patients is feasible. Point-of-care genotyping enables faster de-escalation, reducing bleeding risk and medication costs.
Area of Science:
- Cardiology
- Pharmacogenomics
- Clinical Implementation
Background:
- Current guidelines recommend potent P2Y12 inhibitors (prasugrel, ticagrelor) for acute coronary syndrome (ACS).
- These agents increase bleeding risk compared to clopidogrel.
- Genotype-guided selection can mitigate bleeding risk, but clinical implementation data is limited.
Purpose of the Study:
- To assess the feasibility of CYP2C19 genotype-guided P2Y12 inhibitor de-escalation in ACS patients.
- To compare point-of-care (POC) versus laboratory-based genotyping turnaround times.
- To evaluate physician adherence, time to de-escalation, and cost reduction.
Main Methods:
- Included 738 ACS patients receiving ticagrelor and CYP2C19 genotyping (POC or lab-based).
- Collected data on genotyping turnaround, de-escalation eligibility and timing, physician adherence, and costs.
- Analyzed outcomes based on genotyping method.
Main Results:
- Median genotyping turnaround time was 6.3 hours, with 82.3% results within 24 hours.
- POC genotyping was significantly faster than lab-based (5.7 vs 47.8 hours).
- 81.7% were eligible for de-escalation, achieved within 48 hours in 93.0%; POC led to quicker de-escalation (25.4 vs 58.9 hours).
- Strategy resulted in €211,150.50 medication cost savings.
Conclusions:
- CYP2C19 genotype-guided de-escalation is feasible in ACS patients.
- POC genotyping offers faster turnaround and de-escalation.
- Physician adherence was high, facilitating timely de-escalation to clopidogrel in noncarriers.
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.
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