PATHCHAT Edition
Published: 2024
Please contact your local Ampath pathologist for more information.
Overview of Clopidogrel Therapy and Pharmacogenomics
✅ Dual Antiplatelet Therapy in Coronary Artery Disease (CAD)
- Aspirin + P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is the standard of care for preventing ischemic events.
- Indicated in:
- Acute coronary syndrome (ACS).
- Percutaneous coronary intervention (PCI).
- Clopidogrel is the most commonly prescribed P2Y12 inhibitor due to:
- Favourable safety profile.
- Lower cost compared to ticagrelor or prasugrel.
- Broad indications.
✅ The Problem of High On-Treatment Platelet Reactivity (HPR)
- Approximately 30% of clopidogrel-treated patients experience HPR, which increases thrombotic risk.
- More potent P2Y12 inhibitors (prasugrel, ticagrelor) reduce HPR but have:
- Higher bleeding risks.
- Greater cost.
📌 Pharmacogenomic testing can help identify patients at risk of poor clopidogrel response.
The Role of CYP2C19 Genetic Variability
✅ Genetic Influence on Clopidogrel Metabolism
- Clopidogrel is a prodrug that requires conversion into its active form by the CYP2C19 enzyme.
- Loss-of-function (LoF) variants in CYP2C19 reduce active metabolite production, leading to:
- Increased risk of HPR.
- Higher rates of thrombotic complications.
✅ How Common are CYP2C19 LoF Alleles?
- 30% of individuals carry at least one LoF allele, significantly impacting clopidogrel effectiveness.
📌 Genetic testing identifies LoF carriers who may benefit from alternative antiplatelet therapy.
Meta-Analysis Evidence for Genotype-Guided Therapy
✅ JACC 2021 Meta-Analysis
- Reviewed seven randomised controlled trials (RCTs) involving 15,949 patients.
- Study Population:
- 98% had ACS.
- 77% underwent PCI.
- Findings:
- Using ticagrelor or prasugrel in CYP2C19 LoF carriers significantly reduced ischemic events.
- Selective use of clopidogrel in non-LoF carriers avoided unnecessary bleeding risks.
📌 Genotype-guided therapy reduces ischemic events while minimising bleeding complications.
Genotype-Based Treatment Recommendations
✅ For CYP2C19 LoF Carriers (~30% of patients)
- Preferred treatment: Ticagrelor or prasugrel.
- Risk reduction:
- 30% lower relative risk of ischemic events (RR 0.70; 95% CI 0.59–0.83).
✅ For CYP2C19 Non-LoF Carriers (~70% of patients)
- Clopidogrel remains a safe and effective option.
- No significant ischemic risk compared to ticagrelor/prasugrel (RR 1.00; 95% CI 0.80–1.25).
📌 Genotyping enables personalised therapy, optimising both safety and efficacy.
Genetic Testing for CYP2C19 at Ampath
✅ Test Availability and Details
- CYP2C19 genotyping is included in Ampath’s pharmacogenomics panel (Mnemonic: PHARMA).
- Turnaround time: 10 working days.
- Sample type: Buccal swab or EDTA blood.
✅ How to Order Testing
- For test enquiries or results interpretation, contact:
- Email: pgx@ampath.co.za.
📌 Pharmacogenomic testing optimises clopidogrel prescribing, improving patient outcomes.
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