Preoperative CYP2D6 metabolism-dependent β-blocker use and mortality after coronary artery bypass grafting surgery

Miklos D. Kertai, Stephen A. Esper, Igor Akushevich, Deepak Voora, Geoffrey S. Ginsburg, Mark Stafford-Smith, Katherine Grichnik, Mark F. Newman, Manuel L. Fontes, Peter Smith, Mihai V. Podgoreanu, Joseph P. Mathew

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Abstract

Objective Recently, the role of β-blockers (BBs) in reducing perioperative mortality has been challenged. The conflicting results might have resulted from the extent of BB metabolism by the cytochrome P-450 (CYP2D6) isoenzyme. The purpose of the present study was to assess the association between the preoperative use of BBs dependent on metabolism of the CYP2D6 isoenzyme with operative mortality after coronary artery bypass grafting surgery. Methods We performed a retrospective study of 5248 patients who had undergone coronary bypass grafting surgery from January 1, 2001 to November 30, 2009 at Duke University Medical Center. The cohorts were defined by the preoperative use of BBs and BB type (non-CYP2D6-BBs, CYP2D6-BBs, or no BBs). Operative mortality was analyzed using inverse probability-weighted estimators with propensity score adjustment. Results Of the 5248 patients, 14% received non-CYP2D6-BBs, 43%, CYP2D6-BBs, and 43%, no BBs. The incidence of operative mortality was 0.8%, 2.1%, and 3.7% in the non-CYP2D6-BB, CYP2D6-BB, and no BB groups, respectively. Multivariable inverse probability-weighted-adjusted analyses showed that non-CYP2D6-BBs were associated with a lower incidence of operative mortality (odds ratio, 0.33; 95% confidence interval, 0.13-0.83; P =.02) compared with no BB use and a trend toward lower operative mortality (odds ratio, 0.44; 95% confidence interval, 0.16-1.07; P =.06) compared with CYP2D6-BBs. No significant decrease occurred in the risk of operative mortality between the CYP2D6-BB and no BB groups (odds ratio, 0.85; 95% confidence interval, 0.54-1.34; P =.48). Conclusions Among these patients, preoperative non-CYP2D6-BB use, but not CYP2D6-BB use, was associated with a decreased risk of operative mortality.

Original languageEnglish
Pages (from-to)1368-1375.E3
JournalJournal of Thoracic and Cardiovascular Surgery
Volume147
Issue number4
DOIs
Publication statusPublished - Apr 2014

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ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Kertai, M. D., Esper, S. A., Akushevich, I., Voora, D., Ginsburg, G. S., Stafford-Smith, M., Grichnik, K., Newman, M. F., Fontes, M. L., Smith, P., Podgoreanu, M. V., & Mathew, J. P. (2014). Preoperative CYP2D6 metabolism-dependent β-blocker use and mortality after coronary artery bypass grafting surgery. Journal of Thoracic and Cardiovascular Surgery, 147(4), 1368-1375.E3. https://doi.org/10.1016/j.jtcvs.2013.09.067