CYP2D6 Genotype-guided Metoprolol Therapy in Cardiac Surgery Patients: Rationale and Design of the Pharmacogenetic-guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery (PREEMPTIVE) Pilot Study

Wills C. Dunham, Matthew B. Weinger, Jason Slagle, Mias Pretorius, Ashish S. Shah, Tarek S. Absi, Matthew S. Shotwell, Marc Beller, Erica Thomas, Cindy L. Vnencak-Jones, Robert E. Freundlich, Jonathan P. Wanderer, Warren S. Sandberg, Miklos D. Kertai

Research output: Contribution to journalArticle

Abstract

Objectives: The Preemptive Pharmacogenetic-guided Metoprolol Management for Atrial Fibrillation in Cardiac Surgery (PREEMPTIVE) pilot trial aims to use existing institutional resources to develop a process for integrating CYP2D6 pharmacogenetic test results into the patient electronic health record, to develop an evidence-based clinical decision support tool to facilitate CYP2D6 genotype-guided metoprolol administration in the cardiac surgery setting, and to determine the impact of implementing this CYP2D6 genotype-guided integrated approach on the incidence of postoperative atrial fibrillation (AF), provider, and cost outcomes. Design: One-arm Bayesian adaptive design clinical trial. Setting: Single center, university hospital. Participants: The authors will screen (including CYP2D6 genotype) up to 600 (264 ± 144 expected under the adaptive design) cardiac surgery patients, and enroll up to 200 (88 ± 48 expected) poor, intermediate, and ultrarapid CYP2D6 metabolizers over a period of 2 years at a tertiary academic center. Interventions: All consented and enrolled patients will receive the intervention of CYP2D6 genotype-guided metoprolol management based on CYP2D6 phenotype classified as a poor, intermediate, extensive (normal), or ultrarapid metabolizer. Measurements and Main Results: The primary outcome will be the incidence of postoperative AF. Secondary outcomes relating to rates of CYP2D6 genotype-guided prescription changes, costs, lengths of stay, and implementation metrics also will be investigated. Conclusions: The PREEMPTIVE pilot study is the first perioperative pilot trial to provide essential information for the design of a future, large-scale trial comparing CYP2D6 genotype-guided metoprolol management with a nontailored strategy in terms of managing AF. In addition, secondary outcomes regarding implementation, clinical benefit, safety, and cost-effectiveness in patients undergoing cardiac surgery will be examined.

Original languageEnglish
Pages (from-to)20-28
Number of pages9
JournalJournal of Cardiothoracic and Vascular Anesthesia
Volume34
Issue number1
DOIs
Publication statusPublished - Jan 2020

    Fingerprint

Keywords

  • CYP2D6 polymorphisms
  • atrial fibrillation
  • cardiac surgery
  • clinical decision support tool
  • metoprolol
  • outcomes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Anesthesiology and Pain Medicine

Cite this

Dunham, W. C., Weinger, M. B., Slagle, J., Pretorius, M., Shah, A. S., Absi, T. S., Shotwell, M. S., Beller, M., Thomas, E., Vnencak-Jones, C. L., Freundlich, R. E., Wanderer, J. P., Sandberg, W. S., & Kertai, M. D. (2020). CYP2D6 Genotype-guided Metoprolol Therapy in Cardiac Surgery Patients: Rationale and Design of the Pharmacogenetic-guided Metoprolol Management for Postoperative Atrial Fibrillation in Cardiac Surgery (PREEMPTIVE) Pilot Study. Journal of Cardiothoracic and Vascular Anesthesia, 34(1), 20-28. https://doi.org/10.1053/j.jvca.2019.09.003