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Original Investigation
August 25, 2020

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

Author Affiliations
  • 1Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
  • 2Peter Munk Cardiac Centre and Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto, Ontario, Canada
  • 3University of Ottawa Heart Institute, Ottawa, Ontario, Canada
  • 4Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
  • 5National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
  • 6Department of Medicine, Loyola University, Maywood, Illinois
  • 7Department of Internal Medicine, Division of Cardiology, Konyang University, Seo-gu, Taejon, South Korea
  • 8Heart Research Center, Chonnam National University, Gwangju, South Korea
  • 9Department of Cardiology, Minneapolis Heart Institute Foundation, Minneapolis, Minnesota
  • 10Division of Cardiology, The Miriam Hospital, Providence, Rhode Island
  • 11Division of Cardiology, Rhode Island Hospital, Providence, Rhode Island
  • 12Mayo Clinic Health System—La Crosse, La Crosse, Wisconsin
  • 13Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
  • 14St Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada
  • 15Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta
  • 16Division of Cardiology, Department of Medicine, Albany Medical Center and Albany Medical College, Albany, New York
  • 17Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada
  • 18Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota
  • 19Department of Medicine, Mazankowski Alberta Heart Institute and University of Alberta, Edmonton, Alberta, Canada
JAMA. 2020;324(8):761-771. doi:10.1001/jama.2020.12443
Key Points

Question  Does CYP2C19 genotype–guided prescription of oral P2Y12 inhibitor therapy after percutaneous coronary intervention (PCI) improve ischemic outcomes in patients with acute coronary syndromes and stable coronary artery disease?

Findings  In this randomized clinical trial that included 5302 patients undergoing PCI and included 1849 patients with CYP2C19 loss-of-function alleles in the primary analysis, genotype-guided selection of oral P2Y12 inhibitor therapy, compared with conventional therapy using clopidogrel, resulted in no significant difference in a composite end point of cardiovascular death, myocardial infarction, stroke, stent thrombosis, or severe recurrent ischemia at 12 months (4.0% vs 5.9%, respectively; hazard ratio, 0.66).

Meaning  Among patients with CYP2C19 loss-of-function alleles who underwent PCI, genotype-guided selection of an oral P2Y12 inhibitor, compared with conventional clopidogrel therapy, did not significantly reduce ischemic events based on the treatment effect that the study was powered to detect at 12 months.

Abstract

Importance  After percutaneous coronary intervention (PCI), patients with CYP2C19*2 or *3 loss-of-function (LOF) variants treated with clopidogrel have increased risk of ischemic events. Whether genotype-guided selection of oral P2Y12 inhibitor therapy improves ischemic outcomes is unknown.

Objective  To determine the effect of a genotype-guided oral P2Y12 inhibitor strategy on ischemic outcomes in CYP2C19 LOF carriers after PCI.

Design, Setting, and Participants  Open-label randomized clinical trial of 5302 patients undergoing PCI for acute coronary syndromes (ACS) or stable coronary artery disease (CAD). Patients were enrolled at 40 centers in the US, Canada, South Korea, and Mexico from May 2013 through October 2018; final date of follow-up was October 2019.

Interventions  Patients randomized to the genotype-guided group (n = 2652) underwent point-of-care genotyping. CYP2C19 LOF carriers were prescribed ticagrelor and noncarriers clopidogrel. Patients randomized to the conventional group (n = 2650) were prescribed clopidogrel and underwent genotyping after 12 months.

Main Outcomes and Measures  The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia at 12 months. A secondary end point was major or minor bleeding at 12 months. The primary analysis was in patients with CYP2C19 LOF variants, and secondary analysis included all randomized patients. The trial had 85% power to detect a minimum hazard ratio of 0.50.

Results  Among 5302 patients randomized (median age, 62 years; 25% women), 82% had ACS and 18% had stable CAD; 94% completed the trial. Of 1849 with CYP2C19 LOF variants, 764 of 903 (85%) assigned to genotype-guided therapy received ticagrelor, and 932 of 946 (99%) assigned to conventional therapy received clopidogrel. The primary end point occurred in 35 of 903 CYP2C19 LOF carriers (4.0%) in the genotype-guided therapy group and 54 of 946 (5.9%) in the conventional therapy group at 12 months (hazard ratio [HR], 0.66 [95% CI, 0.43-1.02]; P = .06). None of the 11 prespecified secondary end points showed significant differences, including major or minor bleeding in CYP2C19 LOF carriers in the genotype-guided group (1.9%) vs the conventional therapy group (1.6%) at 12 months (HR, 1.22 [95% CI, 0.60-2.51]; P = .58). Among all randomized patients, the primary end point occurred in 113 of 2641 (4.4%) in the genotype-guided group and 135 of 2635 (5.3%) in the conventional group (HR, 0.84 [95% CI, 0.65-1.07]; P = .16).

Conclusions and Relevance  Among CYP2C19 LOF carriers with ACS and stable CAD undergoing PCI, genotype-guided selection of an oral P2Y12 inhibitor, compared with conventional clopidogrel therapy without point-of-care genotyping, resulted in no statistically significant difference in a composite end point of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia based on the prespecified analysis plan and the treatment effect that the study was powered to detect at 12 months.

Trial Registration  ClinicalTrials.gov Identifier: NCT01742117

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