Meta-analysis of secure randomised controlled trials of beta-blockade to prevent perioperative death in non-cardiac surgery
Author(s)
Bouri, Sonia
Shun-Shin, Matthew James
Cole, Graham D
Mayet, Jamil
Francis, Darrel P
Type
Journal Article
Abstract
Background Current European and American guidelines recommend the perioperative initiation of a course of β-blockers in those at risk of cardiac events undergoing high- or intermediate-risk surgery or vascular surgery. The Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) family of trials, the bedrock of evidence for this, are no longer secure. We therefore conducted a meta-analysis of randomised controlled trials of β-blockade on perioperative mortality, non-fatal myocardial infarction, stroke and hypotension in non-cardiac surgery using the secure data.
Methods The randomised controlled trials of initiation of β-blockers before non-cardiac surgery were examined. Primary outcome was all-cause mortality at 30 days or at discharge. The DECREASE trials were separately analysed.
Results Nine secure trials totalling 10 529 patients, 291 of whom died, met the criteria. Initiation of a course of β-blockers before surgery caused a 27% risk increase in 30-day all-cause mortality (p=0.04). The DECREASE family of studies substantially contradict the meta-analysis of the secure trials on the effect of mortality (p=0.05 for divergence). In the secure trials, β-blockade reduced non-fatal myocardial infarction (RR 0.73, p=0.001) but increased stroke (RR 1.73, p=0.05) and hypotension (RR 1.51, p<0.00001). These results were dominated by one large trial.
Conclusions Guideline bodies should retract their recommendations based on fictitious data without further delay. This should not be blocked by dispute over allocation of blame. The well-conducted trials indicate a statistically significant 27% increase in mortality from the initiation of perioperative β-blockade that guidelines currently recommend. Any remaining enthusiasts might best channel their energy into a further randomised trial which should be designed carefully and conducted honestly.
Methods The randomised controlled trials of initiation of β-blockers before non-cardiac surgery were examined. Primary outcome was all-cause mortality at 30 days or at discharge. The DECREASE trials were separately analysed.
Results Nine secure trials totalling 10 529 patients, 291 of whom died, met the criteria. Initiation of a course of β-blockers before surgery caused a 27% risk increase in 30-day all-cause mortality (p=0.04). The DECREASE family of studies substantially contradict the meta-analysis of the secure trials on the effect of mortality (p=0.05 for divergence). In the secure trials, β-blockade reduced non-fatal myocardial infarction (RR 0.73, p=0.001) but increased stroke (RR 1.73, p=0.05) and hypotension (RR 1.51, p<0.00001). These results were dominated by one large trial.
Conclusions Guideline bodies should retract their recommendations based on fictitious data without further delay. This should not be blocked by dispute over allocation of blame. The well-conducted trials indicate a statistically significant 27% increase in mortality from the initiation of perioperative β-blockade that guidelines currently recommend. Any remaining enthusiasts might best channel their energy into a further randomised trial which should be designed carefully and conducted honestly.
Date Issued
2014-03
Date Acceptance
2013-07-12
Citation
Heart, 2014, 100 (6), pp.456-464
ISSN
1355-6037
Publisher
BMJ Publishing Group
Start Page
456
End Page
464
Journal / Book Title
Heart
Volume
100
Issue
6
Copyright Statement
© The Author(s). This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/
Sponsor
British Heart Foundation
British Heart Foundation
British Heart Foundation
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000331610400006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
FS/10/38/28268
FS/12/12/29294
FS/14/27/30752
Subjects
Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
HIGH-RISK PATIENTS
VASCULAR-SURGERY
MYOCARDIAL-ISCHEMIA
CARDIAC MORTALITY
DECREASE-IV
CR ZOK
METOPROLOL
BISOPROLOL
BLOCKERS
FLUVASTATIN
Publication Status
Published
Date Publish Online
2013-07-31