Reviwer : Dr. Örsan Deniz URGUN

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

Published in Congress : ACC 2021

Full Text Link :  https://jamanetwork.com/journals/jama/article-abstract/2769725

Background : After percutaneous coronary intervention, patients with CYP2C19*2 or *3 loss of-function (LOF) mutations treated with clopidogrel have an increased risk of ischemic events. It is unknown whether genotype-guided selection of oral P2Y12 inhibitor therapy improves ischemic outcomes.

Objective : To determine the effect of oral P2Y12 inhibitor strategy on ischemic outcomes in CYP2C19 LOF carriers following genotype-guided percutaneous coronary intervention.

Method : The study is an open-label, randomized controlled trial. 5302 patients who underwent percutaneous coronary intervention due to acute coronary syndrome and stable coronary artery are included, the mean age of the patients was 62, 25% were female, 82% were applied percutaneous coronary intervention after acute coronary syndrome, 18% diagnosed with stable coronary artery disease; Genotype determination is made in 2652 patients, and CYP2C19 LOF carriers are treated with ticagrelor and non-carriers with clopidogrel, 2650 patients are randomized to conventional therapy and this group is treated with clopidogrel. At the end of 12 months, genotype determination is made in the conventional group. The primary endpoint is 12-month composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia.

Results : While 903 patients in the genotype group were found to be carriers of CYP2C19 LOF, the primary outcome was seen in 35 patients (4.0%) in this group. In the conventional group, 946 patients were found to be carriers of CYP2C19 LOF, and the primary outcome was 54 (5.9%) patients in this group (HR 0.66, 95% CI 0.43-1.02, p=0.06). Major or minor bleeding was similar in the two groups.

Conclusion : Genotype-guided P2Y12 inhibitor selection was not found to be superior to conventional clopidogrel use in patients undergoing percutaneous coronary intervention.

Interpretation : This is the first clinical trial to our knowledge to prospectively address the potential benefit of genotype-guided oral P2Y12 inhibitor therapy compared to conventional therapy. DUAL antiplatelet therapy is the standard treatment method to reduce stent thrombosis and ischemic events after percutaneous coronary intervention.
Changes in stent designs and new drugs are developing to reduce stent thrombosis.
While genetic guidance research continues; research is needed to detect drug resistance with techniques that are easily accessible and affordable to the clinician.