title: Preoperative CYP2D6 metabolism-dependent β-blocker use and mortality after coronary artery bypass grafting surgery.
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.
authors.affiliation: Division of Cardiothoracic Anesthesiology and Critical Care, Department of Anesthesiology, Duke University Medical Center, Durham, NC. Electronic address: miklos.kertai@duke.edu.
authors.forename: Miklos D
authors.initials: MD
authors.lastname: Kertai
authors.affiliation: Division of Cardiovascular and Thoracic Anesthesiology, Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, Pa.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Esper
authors.affiliation: Center for Population Health and Aging, Duke University Medical Center, Durham, NC.
authors.forename: Igor
authors.initials: I
authors.lastname: Akushevich
authors.affiliation: Duke Institute for Genome Science and Policy, Duke University Medical Center, Durham, NC.
authors.forename: Deepak
authors.initials: D
authors.lastname: Voora
authors.affiliation: Duke Institute for Genome Science and Policy, Duke University Medical Center, Durham, NC.
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Ginsburg
authors.affiliation: Division of Cardiothoracic Anesthesiology and Critical Care, Department of Anesthesiology, Duke University Medical Center, Durham, NC.
authors.forename: Mark
authors.initials: M
authors.lastname: Stafford-Smith
authors.affiliation: Division of Cardiothoracic Anesthesiology and Critical Care, Department of Anesthesiology, Duke University Medical Center, Durham, NC.
authors.forename: Katherine
authors.initials: K
authors.lastname: Grichnik
authors.affiliation: Division of Cardiothoracic Anesthesiology and Critical Care, Department of Anesthesiology, Duke University Medical Center, Durham, NC.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Newman
authors.affiliation: Division of Cardiothoracic Anesthesiology and Critical Care, Department of Anesthesiology, Duke University Medical Center, Durham, NC.
authors.forename: Manuel L
authors.initials: ML
authors.lastname: Fontes
authors.affiliation: Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC.
authors.forename: Peter
authors.initials: P
authors.lastname: Smith
authors.affiliation: Division of Cardiothoracic Anesthesiology and Critical Care, Department of Anesthesiology, Duke University Medical Center, Durham, NC.
authors.forename: Mihai V
authors.initials: MV
authors.lastname: Podgoreanu
authors.affiliation: Division of Cardiothoracic Anesthesiology and Critical Care, Department of Anesthesiology, Duke University Medical Center, Durham, NC.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mathew
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D001026:Coronary Artery Bypass / Q000401:mortality*; D019389:Cytochrome P-450 CYP2D6 / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D012189:Retrospective Studies
chemical_list: D000319:Adrenergic beta-Antagonists; D019389:Cytochrome P-450 CYP2D6