Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection vs Conventional Clopidogrel Therapy on Ischemic Outcomes After Percutaneous Coronary Intervention: The TAILOR-PCI Randomized Clinical Trial

RCT (n=5,302) found that genotype-guided P2Y12 inhibitor selection did not improve the composite end point of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischaemia vs conventional clopidogrel without genotype testing.

SPS commentary:

In the genotype guided arm, patients with CYP2C19 loss of function genetic carriers were allocated ticagrelor, whereas non-carriers were given clopidogrel.

A related editorial comments that, following the results of the study, the important question is why has such a muted benefit been recurrently observed despite such a scientifically logical approach? It seems intuitive that escalating to more potent P2Y12 therapy for patients who are poor clopidogrel metabolizers and deescalating to clopidogrel for patients who are efficient metabolizers should optimize the effectiveness and safety of DAPT beyond a onesize-fits-all approach.


Points to consider, include the fact that having loss of function alleles does not necessarily indicate inadequate platelet inhibition for a particular individual. The risk-benefit ratio of antithrombotic therapy depends on the intensity and duration of the therapy as well as the intensity and duration of the clinical condition. Second, advances in medical therapy, stent technology, and procedural techniques may have diminished the need for more intensive antithrombotic therapy, particularly beyond the first 3 months after PCI, when the rates of ischemic events are declining. Third, while clopidogrel metabolism plays an undeniable part in the response to therapy and subsequently the rate of clinical events, other important epigenetic and patient-related factors have a larger role. Factors such as drug absorption, adherence to therapy, patient comorbidities, and coronary anatomical and interventional procedural factors account for the majority of ischaemic events.


Authors of the editorial conclude that the utility of a personalised medicine approach as attempted by genotyping for drug response should not be abandoned in modern practice.  The future is clearly pointing toward a personalised strategy for therapeutic interventions, and genotype-guided approaches should be part of this strategy—the question is how much. However, the clinical evidence at this critical moment of revamping the health care system does not support the routine use of personalized genotype-based selection of antiplatelet therapy for patients with coronary artery disease.


Journal of the American Medical Association

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