Genotype-Guided P2Y12 Inhibitor Therapy after Percutaneous Coronary Intervention: A Bayesian Analysis

Vibhu Parcha, Brittain F. Heindl, Peng Li, Rajat Kalra, Nita A. Limdi, Naveen L. Pereira, Garima Arora, Pankaj Arora

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6 Scopus citations

Abstract

BACKGROUND: Among patients receiving percutaneous coronary intervention (PCI), the role of a genotype-guided approach for antiplatelet therapy compared with usual care is unclear. We conducted a Bayesian analysis of the entire TAILOR-PCI (Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention) randomized clinical trial population to evaluate the effect of the genotype-guided antiplatelet therapy post-PCI compared with the usual care on the risk of major adverse cardiovascular events (MACE). METHODS: The primary outcome for our study was the composite of MACE (myocardial infarction, stroke, and cardiovascular death). Secondary outcomes included cardiovascular death, stroke, myocardial infarction, stent thrombosis, and major/minor bleeding. Bayesian modeling was used to estimate the probability of clinical benefit of genotype-guided therapy using (1) noninformative priors (ie, analyzing the TAILOR-PCI trial) and (2) informative priors derived from the ADAPT, POPular Genetics, IAC-PCI, and PHARMCLO trials (ie, analyzing TAILOR-PCI trial in the context of prior evidence). Risk ratio (RR: ratio of cumulative outcome incidence between genotype-guided and conventional therapy group) and 95% credible interval (CrI) were estimated for the study outcomes, and probability estimates for RR <1 were computed. RESULTS: Using noninformative priors, in TAILOR-PCI the RR for MACE was 0.78 (95% CrI, 0.55–1.07) in genotype-guided therapy after PCI, and the probability of RR <1 was 94%. Using noninformative priors, the probability of RR <1 for cardiovascular death (RR, 0.95 [95% CrI, 0.52–1.74]), stroke (RR, 0.68 [95% CrI, 0.44–1.06]), myocardial infarction (RR, 0.84 [95% CrI, 0.37–1.89]), stent thrombosis (RR, 0.75 [95% CrI, 0.37–1.45]), and major or minor bleeding (RR, 1.22 [95% CrI, 0.84–1.77]) were 57%, 96%, 67%, 81%, and 15%, respectively. Using informative priors, the posterior probability of RR <1 for MACE, from genotype-guided therapy, was 99% (RR, 0.69 [95% CrI, 0.57–0.84]). Using informative priors, the posterior probability of RR <1 for cardiovascular death (RR, 0.86 [95% CrI, 0.61–1.19]), stroke (RR, 0.69 [95% CrI, 0.48–0.99]), myocardial infarction (RR:0.56 [95% CrI, 0.40–0.78]), stent thrombosis (RR, 0.59 [95% CrI, 0.38–0.94]), and major or minor bleeding (RR, 0.84 [95% CrI, 0.70–0.99]) were 81%, 99%, 99%, 99%, and 99%, respectively. CONCLUSIONS: Bayesian analysis of the TAILOR-PCI trial provides clinically meaningful data on the posterior probability of reducing MACE using genotype-guided P2Y12 inhibitor therapy after PCI.

Original languageEnglish (US)
Pages (from-to)731-739
Number of pages9
JournalCirculation: Genomic and Precision Medicine
Volume14
Issue number6
DOIs
StatePublished - Dec 1 2021

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health Mentored Patient-Oriented Research Award (5K23HL146887-03) to Dr Arora. Dr Pereira is supported by the National Institutes of Health Award 3U01HL128606-03S1 and U01 HL128606.

Publisher Copyright:
© 2021 American Heart Association, Inc.

Keywords

  • Genomics
  • Genotype
  • Myocardial infarction
  • Percutaneous coronary intervention
  • Pharmacogenetics
  • Stent
  • Thrombosis

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