Current European guidelines recommend the perioperative initiation of a course of beta-blockers in those at risk of cardiac events undergoing high- or intermediate-risk surgery or vascular surgery (a class I/IIa recommendation). The mortality benefit of this approach is based on data from the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) family of trials. These trials were discredited because of various serious flaws but the European Society of Cardiology (ESC) guidelines, which are based on DECREASE data, have not been retracted.
The current meta-analysis therefore focused on the remaining ‘secure’ randomised controlled trials investigating the initiation of a course of beta-blockers for the prevention of all-cause mortality (30 days or until hospital discharge; primary endpoint) in patients undergoing non-cardiac surgery.
A total of nine ‘secure’ RCTs (n= 10, 529) met the eligibility criteria with 162 deaths reported in 5,264 patients randomised to beta-blockers (bisoprolol, metoprolol, atenolol, propranolol) and 129 deaths reported in 5,265 patients randomised to placebo. In these studies, beta-blockers demonstrated a statistically and clinically significant relative increase in mortality of 27% (RR 1.27, 95% CI 1.01% to 1.60%, p=0.04). There was little heterogeneity between studies (I2=0%, p=0.68). Furthermore, the contrast between the secure and the DECREASE studies was statistically significant (p=0.05).
The authors note that without the inclusion of the DECREASE studies, the current meta-analysis is heavily influenced by the POISE trial. This trial initiated a dose considered by some to be high (100 mg extended-release metoprolol) shortly before surgery. This has been argued to be unrepresentative of clinical practice.
The authors note that if the appropriateness of the POISE protocol is doubted, then the remaining secure data are not sufficient to guide physicians either way.
They suggest that the current ESC guidelines for perioperative beta-blocker initiation should be retracted and that “routine initiation of beta-blockers for this indication should not be recommended, except in the context of RCTs which should be designed carefully, conducted honestly and reported truthfully.”