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

doi:10.1016/j.jtcvs.2013.09.067

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

Anesthesiology

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

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 language	English
Pages (from-to)	1368-1375.E3
Journal	Journal of Thoracic and Cardiovascular Surgery
Volume	147
Issue number	4
DOIs	https://doi.org/10.1016/j.jtcvs.2013.09.067
State	Published - Apr 2014

Bibliographical note

Funding Information:
Disclosures: Dr Smith reports consulting fees from CSL Behring. Dr Newman reports grant support from Merck. Dr Ginsburg reports consulting fees from Pappas ventures, TheHeart.org, Medscape, and Universal Oncology as well as equity ownership in CardinalDx and Universal Oncolgy. All other authors have nothing to disclose with regard to commercial support.

ASJC Scopus subject areas

Surgery
Pulmonary and Respiratory Medicine
Cardiology and Cardiovascular Medicine

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10.1016/j.jtcvs.2013.09.067

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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

@article{0bb7f8baf7534515b70cb960bdc7e3e8,

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.",

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

note = "Funding Information: Disclosures: Dr Smith reports consulting fees from CSL Behring. Dr Newman reports grant support from Merck. Dr Ginsburg reports consulting fees from Pappas ventures, TheHeart.org, Medscape, and Universal Oncology as well as equity ownership in CardinalDx and Universal Oncolgy. All other authors have nothing to disclose with regard to commercial support. ",

year = "2014",

month = apr,

doi = "10.1016/j.jtcvs.2013.09.067",

language = "English",

volume = "147",

pages = "1368--1375.E3",

number = "4",

}

Kertai, MD, Esper, SA, Akushevich, I, Voora, D, Ginsburg, GS, Stafford-Smith, M, Grichnik, K, Newman, MF, Fontes, ML, Smith, P, Podgoreanu, MV & Mathew, JP 2014, 'Preoperative CYP2D6 metabolism-dependent β-blocker use and mortality after coronary artery bypass grafting surgery', Journal of Thoracic and Cardiovascular Surgery, vol. 147, no. 4, pp. 1368-1375.E3. https://doi.org/10.1016/j.jtcvs.2013.09.067

TY - JOUR

T1 - Preoperative CYP2D6 metabolism-dependent β-blocker use and mortality after coronary artery bypass grafting surgery

AU - Kertai, Miklos D.

AU - Esper, Stephen A.

AU - Akushevich, Igor

AU - Voora, Deepak

AU - Ginsburg, Geoffrey S.

AU - Stafford-Smith, Mark

AU - Grichnik, Katherine

AU - Newman, Mark F.

AU - Fontes, Manuel L.

AU - Smith, Peter

AU - Podgoreanu, Mihai V.

AU - Mathew, Joseph P.

N1 - Funding Information: Disclosures: Dr Smith reports consulting fees from CSL Behring. Dr Newman reports grant support from Merck. Dr Ginsburg reports consulting fees from Pappas ventures, TheHeart.org, Medscape, and Universal Oncology as well as equity ownership in CardinalDx and Universal Oncolgy. All other authors have nothing to disclose with regard to commercial support.

PY - 2014/4

Y1 - 2014/4

N2 - 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.

AB - 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.

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DO - 10.1016/j.jtcvs.2013.09.067

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AN - SCOPUS:84896541943

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VL - 147

SP - 1368-1375.E3

JO - Journal of Thoracic and Cardiovascular Surgery

JF - Journal of Thoracic and Cardiovascular Surgery

IS - 4

ER -

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

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