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.

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Published Version (Please cite this version)

10.1016/j.jtcvs.2013.09.067

Publication Info

Kertai, Miklos D, Stephen A Esper, Igor Akushevich, Deepak Voora, Geoffrey S Ginsburg, Mark Stafford-Smith, Katherine Grichnik, Mark F Newman, et al. (2014). Preoperative CYP2D6 metabolism-dependent β-blocker use and mortality after coronary artery bypass grafting surgery. J Thorac Cardiovasc Surg, 147(4). pp. 1368–1375.e3. 10.1016/j.jtcvs.2013.09.067 Retrieved from https://hdl.handle.net/10161/14831.

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Scholars@Duke

Igor Akushevich

Research Professor in the Social Science Research Institute
Voora

Deepak Voora

Associate Professor of Medicine
Ginsburg

Geoffrey Steven Ginsburg

Adjunct Professor in the Department of Medicine

Dr. Geoffrey S. Ginsburg's research interests are in the development of novel paradigms for developing and translating genomic information into medical practice and the integration of personalized medicine into health care.

Stafford-Smith

Mark Stafford-Smith

Professor Emeritus of Anesthesiology

My research interests are in the area of Cardiothoracic Anesthesiology. The main focus of my research is towards the understanding and prevention of acute kidney injury after cardiac and other major surgeries. Secondary interests include the study of analgesic strategies after cardiothoracic surgical procedures, performance of clinical trials, and perioperative transfusion and hemostasis.

Newman

Mark Franklin Newman

Merel H. Harmel Distinguished Professor Emeritus of Anesthesiology

Best known for his work in assessing and improving clinical outcomes and quality of life following cardiac surgery, Dr. Mark Newman is President of the Duke Private Diagnostic Clinic (The Duke Faculty Practice Organization) and the Merel H. Harmel Professor of Anesthesiology at Duke University Medical Center. In addition, Dr. Newman developed the Multicenter Perioperative Outcomes Research Group of the Duke Clinical Research Institute established at Duke in 2001 to further the study of strategies to improve the outcomes of patients undergoing surgery and anesthesia. Dr. Newman has received funding from the National Institute on Aging, the American Heart Association, the National Heart, Lung and Blood Institute, the Anesthesia Patient Safety Foundation, and the International Anesthesia Research Society  to investigate the impact of perioperative outcomes (neurocognitive decline, stroke, myocardial infarction, renal injury) on quantity and quality of life following cardiac surgery and resulting in numerous seminal publications in the New England Journal of Medicine, JAMA and Lancet. Dr. Newman is a popular lecturer and speaker, having appeared on NBC Nightly News and The Today Show and having spoken at more than 200 national and international meetings.  Dr. Newman recently stepped down as the Chairman of the Duke University Department after 13 years to assume the role of PDC President.  During Dr. Newman’s tenure the department grew exponentially doubling its clinical and academic funding, and developing many outstanding individuals that have gone on to leadership roles at Duke and other key academic institutions across the country.

Podgoreanu

Mihai V. Podgoreanu

Associate Professor of Anesthesiology

Basic-Translational:
1. Systems biology approaches to modeling perioperative cardiovascular injury and adaptation.
2. Mechanisms of perioperative myocardial injury; functional genomics applied to perioperative myocardial injury.
3. Metabolic consequences of perioperative myocardial ischemia-reperfusion injury.
4. Animal models and comparative genomic approaches to study perioperative myocardial ischemia-reperfusion injury.
5. Functional genomics of vein graft disease.
6. Animal models of vein graft disease.
7. Genetic association studies in perioperative medicine.
8. Clinico-genomic risk prediction models for perioperative and long-term adverse cardiovascular outcomes following cardiac surgery.

Clinical:
9. Intraoperative quantification of tissue perfusion by contrast echocardiography.
10. Use of myocardial tissue deformation indices to characterize perioperative ventricular dysfunction/stunning
11. 3-D echocardiographic evaluation of the right ventricle

Mathew

Joseph P. Mathew

Jerry Reves, M.D. Distinguished Professor of Cardiac Anesthesiology

Current research interests include:
1. The relationship between white matter patency, functional connectivity (fMRI) and neurocognitive function following cardiac surgery.
2. The relationship between global and regional cortical beta-amyloid deposition and postoperative cognitive decline.
3. The effect of lidocaine infusion upon neurocognitive function following cardiac surgery.
4. The association between genotype and outcome after cardiac surgery.
5. Atrial fibrillation following cardiopulmonary bypass.


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