Key result
Genotype-guided P2Y12 inhibitor selection reduced ischemic events in CYP2C19 LOF carriers by 34% but did not reach statistical significance (HR 0.66; p=0.06) in the TAILOR-PCI trial.
Why the study?
Debates persist regarding the CYP2C19-mediated metabolism of clopidogrel, and clinical trials on genotype- or platelet function test-guided strategies have yielded inconclusive results or limited benefit.
Does genotype- or PFT-guided antiplatelet therapy improve clinical outcomes compared to unguided therapy in patients with coronary artery disease?
Does genotype- or PFT-guided antiplatelet therapy improve clinical outcomes compared to unguided therapy in patients with coronary artery disease?
Effect estimate: HR 0.66 (95% CI 0.43–1.02)
Absolute Event Rate: 4% vs 5.9%
p-value: p=0.06
Clinicians should prioritize comprehensive patient assessment over single biomarker testing (genotype or PFT) when making antiplatelet therapy decisions, as guided strategies have not consistently shown clinical benefit.
Does not support routine genotype-guided P2Y12 selection; leaves open targeted testing in high-risk CYP2C19 LOF carriers.
In patients with coronary artery disease, antiplatelet therapy is crucial for secondary prevention. Among the available P2Y12 inhibitors, clopidogrel is frequently preferred owing to its favourable safety profile and extensive clinical experience. Nevertheless, debates persist regarding its CYP2C19-mediated metabolism. While a number of clinical trials have been conducted to explore correlations between genotype and clinical outcomes, results have not been conclusive. Subsequent trials on platelet function test (PFT)-guided strategies showed limited benefit. International guidance, including the recent 2023 European Society of Cardiology guidelines for the management of acute coronary syndromes, question the clinical value of genotyping or PFT-guided antiplatelet strategies. Emphasising comprehensive patient profiles over genotype or PFT alone may better balance bleeding and ischaemic risks in antiplatelet therapy.
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Liang et al. (2025) conducted a review in Patients with coronary artery disease including acute coronary syndrome and chronic coronary syndrome undergoing percutaneous coronary intervention. Guided selection or unguided de-escalation of P2Y12 inhibitor therapy (including genotype-guided and platelet function test-guided strategies) vs. Standard dual antiplatelet therapy with potent P2Y12 inhibitors (e.g., ticagrelor or prasugrel) was evaluated on Composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, or severe recurrent ischemia (varied by trial) (HR 0.66, 95% CI 0.43–1.02, p=0.06). Genotype-guided P2Y12 inhibitor selection reduced ischemic events in CYP2C19 LOF carriers by 34% but did not reach statistical significance (HR 0.66; p=0.06) in the TAILOR-PCI trial.
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