Laboratory-based CYP2C19 genotype testing to optimise the effectiveness of antiplatelet therapy for patients experiencing acute ischaemic stroke or transient ischaemic attack

Pilot phase

For an initial pilot phase of this project, we used innovation funding from Tayside health board to request genotype testing for the indicated population (600-800 patients per year) managed by the Acute Stroke Service for whom following an ischaemic stroke or TIA, antiplatelet therapy was indicated. This initiative was commenced in April 2022.

CYP2C19 Genotyping

Genotyping is performed by the NHS Tayside East of Scotland Regional Genetic Laboratory which validated the CYP2C19 assay using TaqMan technology to identify the LOF variants c.681G>A (CYP2C19*2) and c.636G>A (CYP2C19*3) and a gain of function variant c.-806C>T (CYP2C19*17). Tayside request these LOF variants as they are the most commonly occurring and are the ones the clinical evidence is based upon. In Tayside, it is not currently cost effective to test for rare and specific genotypes. However as genomic medicine becomes more commonplace in the future, array based technologies may mean that all variants will be automatically available.

A reporting template was collaboratively developed between the laboratory, clinicians and pharmacist. In order to ensure appropriate understanding of the results, in addition to detailing phenotype and genotype information, the report prominently displays straightforward clinical decision support allowing for easy clinician interpretation of the genotyping test and its implications on the clopidogrel pathway:

  • Clopidogrel Metabolism NOT impaired: clopidogrel use is appropriate in this patient

  • Impaired Clopidogrel Metabolism: select alternative clinically appropriate antiplatelet treatment

Clinical pathway

Alternative antiplatelet options were reviewed and based on existing clinical evidence and following national guidelines the combination of aspirin 75mg once daily and dipyridamole MR 200mg twice a day was identified as an alternative to be used in patients identified as having impaired Clopidogrel Metabolism subject to clinician review. An application was made to the Tayside Medicines Advisory Group for updated indications in patients with genetically determined impaired clopidogrel metabolism. The local area prescribing formulary was then updated. Later and in line with new Royal College of Physician's national stroke guidelines (2023) Ticagrelor also became an alternative.

Target patients were identified as those presenting to Ninewells hospital with an acute ischaemic (non-cardioembolic) stroke or TIA with a likely indication for long term clopidogrel therapy. Either admitted to hospital or referred for outpatient assessment via a TIA clinic. They would be assessed and reviewed by the medical team and the specialist stroke clinical pharmacist. Once relevant patients were identified, genotyping tests were ordered along with other routine tests on the standard electronic test requesting system used within our health board (ICE by Sunquest). The reason for the blood test was explained to the patient, verbal consent obtained and the sample sent to the NHS Tayside Genetic laboratory. Antiplatelet treatment was initiated as per standard care whilst waiting for the test to be reported.

Genotyping reports from the laboratory were sent to the requesting clinician by email and also added electronically to the patient's medical record accessible by both primary and secondary care. Reporting time from sample being received by the laboratory to report generation varied between 5-7 days.

These individual reports would be collaboratively reviewed by the requesting clinician and specialist stroke pharmacist, if the patient was still an in patient, and antiplatelet medication optimised based on the test result. For patients identified as impaired metabolisers who had already been discharged home, optimised antiplatelet medication advice would be communicated to the primary care team. The NHS Tayside stroke nurse liaison team provided further crucial follow-up to patients post discharge from the stroke ward. They not only contributed to ensuring patients were optimised on the appropriate antiplatelet medicine (if this had not happened whilst an in patient) but they also identified those patients which were not genotyped whilst in-patients but should have been. This team would liaise with the stroke pharmacist to have missing tests ordered, reviewed and actioned.

Clinical pathway flowchart

Education

The pathway was disseminated to the medical team and other healthcare professionals (HCP) involved in the care of stroke patients in formal and informal educational sessions delivered in a blended format: face-to-face and online, targeting both primary and secondary care HCP.

The clinical project lead and the clinical pharmacist developed targeted educational sessions for: stroke consultants and senior decision makers; junior doctors; stroke nurse liaison team and pharmacists based in both primary care and secondary care and in the community.

Engagement of the senior members of the stroke team was critical as this ensured early adoption of the initiative and vertical dissemination amongst the medical team. As junior doctors rotated through the stroke department they were inducted to this initiative and it became part of their way of working.

To raise awareness of the initiative and support a successful transition of care, educational sessions were also developed for primary care and community pharmacists as well as pharmacy technicians.

Patient leaflets were created to aid communication with patients.

Implementation

The pharmacist and pharmacy technician, as part of their roles have an early clinical role in the patient's admission to hospital, usually in the first 24 hours. Amongst other activities: completing medicines reconciliation, medication review and participating in daily ward rounds. Pharmacists have the skills and are ideally placed to identify patients with an early indication for clopidogrel: where CT scans have excluded haemorrhagic stroke; and don't have an history of AF. In this initiative the clinical pharmacist could independently request the genotyping tests as well as participate in ward rounds raising awareness about this genotyping initiative and educating and supporting junior and senior doctors in adopting this test into their work routine.

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