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Table 1.  
Patient and Operative Characteristicsa
Patient and Operative Characteristicsa
Table 2.  
Risk-Adjusted Odds Ratios for Early Postoperative Outcomes
Risk-Adjusted Odds Ratios for Early Postoperative Outcomes
1.
Poldermans  D, Boersma  E, Bax  JJ,  et al; Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group.  The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery.  N Engl J Med. 1999;341(24):1789-1794.PubMedGoogle ScholarCrossref
2.
Ferguson  TB  Jr, Coombs  LP, Peterson  ED; Society of Thoracic Surgeons National Adult Cardiac Surgery Database.  Preoperative beta-blocker use and mortality and morbidity following CABG surgery in North America.  JAMA. 2002;287(17):2221-2227.PubMedGoogle ScholarCrossref
3.
Bouri  S, Shun-Shin  MJ, Cole  GD, Mayet  J, Francis  DP.  Meta-analysis of secure randomised controlled trials of β-blockade to prevent perioperative death in non-cardiac surgery.  Heart. 2014;100(6):456-464.PubMedGoogle ScholarCrossref
4.
Devereaux  PJ, Yang  H, Yusuf  S,  et al; POISE Study Group.  Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial.  Lancet. 2008;371(9627):1839-1847.PubMedGoogle ScholarCrossref
5.
Ray  KK, Cannon  CP.  The potential relevance of the multiple lipid-independent (pleiotropic) effects of statins in the management of acute coronary syndromes.  J Am Coll Cardiol. 2005;46(8):1425-1433.PubMedGoogle ScholarCrossref
6.
Durazzo  AE, Machado  FS, Ikeoka  DT,  et al.  Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial.  J Vasc Surg. 2004;39(5):967-975.PubMedGoogle ScholarCrossref
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Research Letter
April 2016

Addition of Statins to Treatment With β-Blockers to Improve Outcomes for Cardiac Surgery Patients: Beyond the Surgical Care Improvement Project

Author Affiliations
  • 1Division of Cardiac Surgery, David Geffen School of Medicine at University of California, Los Angeles
JAMA Surg. 2016;151(4):389-391. doi:10.1001/jamasurg.2015.4212

For nearly 2 decades, β-blockers have been thought to reduce the risk of major adverse cardiovascular events during the perioperative period. Beginning with the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography trial1 in 1999, a series of studies have provided compelling evidence that patients undergoing high-risk operations should receive β-blockers before surgery.2 Given these findings, the Surgical Care Improvement Project required that all patients previously receiving β-blockers should receive their medication in the 24 hours before surgery. More recently, however, several large-scale studies have failed to reproduce these beneficial effects,3,4 and the Perioperative Ischemic Evaluation trial4 found increased mortality with the use of β-blockers before surgery.

A similar controversy exists with regard to the perioperative administration of statins, agents that may reduce cardiovascular events via pleotropic effects.5 Small trials have shown that the use of statins reduces the risk of major adverse cardiovascular events in patients undergoing cardiac surgery.6 Statin use has not been incorporated into the Surgical Care Improvement Project or into the recommendations from professional societies. In the present study, we aim to determine whether treatment with β-blockers, statins, or both before cardiac surgery is associated with a reduction in the risk of adverse events after surgery.

Methods

This study was a retrospective review of our institution’s Society of Thoracic Surgeons database including all adult patients undergoing cardiac surgery between 2008 and 2014 (N = 3826). Patients were divided into 4 groups: no treatment, treatment with β-blockers alone, treatment with statins alone, and treatment with both statins and β-blockers, in the 24 hours preceding surgery. Patients were excluded if they were treated with extracorporeal membrane oxygenation, used ventricular assist devices, received a transplant, had a prior history of arrhythmia, trauma, minor procedures (defined as surgery time of <90 minutes), preoperative intubation, off-pump cases, and incomplete records. Demographic or clinical variables found to have modest significance on univariate analysis (P < .20) were included in a multivariate regression model and are listed in Table 1. The primary end point was in-hospital mortality, while several secondary outcomes (including length of hospital stay, prolonged mechanical ventilation, reoperation for bleeding, postoperative atrial fibrillation, renal failure, and cardiac arrest) were considered. Findings were considered to be statistically significant if P < .05. The study protocol was approved by the institutional review board at the University of California, Los Angeles, and waiver of consent was obtained.

Results

A total of 1930 patients met the inclusion criteria and were divided as follows: 424 patients were treated with β-blockers alone (22%), 278 patients were treated with statins alone (14%), 766 patients were treated with both statins and β-blockers (40%), and 462 patients received no treatment (24%). Group characteristics are displayed in Table 1. After adjustment for baseline differences, mortality rates were similar among all patient groups. No significant differences were seen in secondary outcome measures with either use of β-blockers alone or use of statins alone. However, when compared with the patients who received no treatment, the patients who were treated with both statins and β-blockers had lower rates of prolonged hospitalization (adjusted odds ratio, 0.59 [95% CI, 0.39-0.90]; P = .01), prolonged mechanical ventilation (adjusted odds ratio, 0.61 [95% CI, 0.40-0.92]; P = .02), and reoperations for bleeding (adjusted odds ratio, 0.43 [95% CI, 0.22-0.85]; P = .02) (Table 2).

Discussion

Once a mainstay of therapy, perioperative β-blockade has recently been questioned as appropriate therapy for cardiac surgery patients. The present study also failed to demonstrate improvements in postoperative outcomes with the preoperative administration of β-blockers alone. After adjustment for patient risk factors and differences between treatment groups, we found that the coadministration of β-blockers with statins was associated with improvements in duration of ventilation, length of hospital stay, and the need for reoperation for bleeding. Mechanistically, both classes of medications may reduce the oxidative stress, and β-blockers may reduce the adrenergic surge associated with cardiac surgery.

Our study has several limitations inherent to its retrospective nature. Baseline differences in the characteristics of treatment groups were accounted for using a multivariate model. In addition, our study was not powered to perform subgroup analyses on, for example, coronary bypass operations. Current evidence, although limited, suggests that combination therapy with statins and β-blockers should be considered as a quality metric for cardiac surgery. Future prospective randomized studies are warranted to assess the effects of this combination therapy in larger cohorts.

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Article Information

Corresponding Author: Peyman Benharash, MD, Division of Cardiac Surgery, David Geffen School of Medicine at University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90095 (pbenharash@mednet.ucla.edu).

Published Online: November 18, 2015. doi:10.1001/jamasurg.2015.4212.

Author Contributions: Dr Benharash had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Toppen, Sareh, Satou, Benharash.

Acquisition, analysis, or interpretation of data: Toppen, Sareh, Johansen, Genovese, Shemin, Benharash.

Drafting of the manuscript: Toppen, Sareh, Genovese, Satou.

Critical revision of the manuscript for important intellectual content: Toppen, Sareh, Johansen, Genovese, Shemin, Benharash.

Statistical analysis: Toppen, Sareh, Johansen, Shemin.

Administrative, technical, or material support: Satou, Shemin, Benharash.

Study supervision: Benharash.

Conflict of Interest Disclosures: None reported.

References
1.
Poldermans  D, Boersma  E, Bax  JJ,  et al; Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group.  The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery.  N Engl J Med. 1999;341(24):1789-1794.PubMedGoogle ScholarCrossref
2.
Ferguson  TB  Jr, Coombs  LP, Peterson  ED; Society of Thoracic Surgeons National Adult Cardiac Surgery Database.  Preoperative beta-blocker use and mortality and morbidity following CABG surgery in North America.  JAMA. 2002;287(17):2221-2227.PubMedGoogle ScholarCrossref
3.
Bouri  S, Shun-Shin  MJ, Cole  GD, Mayet  J, Francis  DP.  Meta-analysis of secure randomised controlled trials of β-blockade to prevent perioperative death in non-cardiac surgery.  Heart. 2014;100(6):456-464.PubMedGoogle ScholarCrossref
4.
Devereaux  PJ, Yang  H, Yusuf  S,  et al; POISE Study Group.  Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial.  Lancet. 2008;371(9627):1839-1847.PubMedGoogle ScholarCrossref
5.
Ray  KK, Cannon  CP.  The potential relevance of the multiple lipid-independent (pleiotropic) effects of statins in the management of acute coronary syndromes.  J Am Coll Cardiol. 2005;46(8):1425-1433.PubMedGoogle ScholarCrossref
6.
Durazzo  AE, Machado  FS, Ikeoka  DT,  et al.  Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial.  J Vasc Surg. 2004;39(5):967-975.PubMedGoogle ScholarCrossref
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