BACKGROUND: Beta-blockers are widely used for many cardiovascular conditions; however, their efficacy in contemporary clinical practice remains uncertain.
METHODS: We performed a prospectively designed, umbrella review of meta-analyses of randomised controlled trials (RCTs) investigating the evidence of beta-blockers in the contemporary management of coronary artery disease (CAD), heart failure (HF), patients undergoing surgery or hypertension (registration: PROSPERO CRD42016038375). We searched MEDLINE, EMBASE and the Cochrane Library from inception until December 2018. Outcomes were analysed as beta-blockers versus control for all-cause mortality, myocardial infarction (MI), incident HF or stroke. Two independent investigators abstracted the data, assessed the quality of the evidence and rated the certainty of evidence.
RESULTS: We identified 98 meta-analyses, including 284 unique RCTs and 1,617,523 patient-years of follow-up. In CAD, 12 meta-analyses (93 RCTs, 103,481 patients) showed that beta-blockers reduced mortality in analyses before routine reperfusion, but there was a lack of benefit in contemporary studies where ≥ 50% of patients received thrombolytics or intervention. Beta-blockers reduced incident MI at the expense of increased HF. In HF with reduced ejection fraction, 34 meta-analyses (66 RCTs, 35,383 patients) demonstrated a reduction in mortality and HF hospitalisation with beta-blockers in sinus rhythm, but not in atrial fibrillation. In patients undergoing surgery, 23 meta-analyses (89 RCTs, 19,211 patients) showed no effect of beta-blockers on mortality for cardiac surgery, but increased mortality in non-cardiac surgery. In non-cardiac surgery, beta-blockers reduced MI after surgery but increased the risk of stroke. In hypertension, 27 meta-analyses (36 RCTs, 260,549 patients) identified no benefit versus placebo, but beta-blockers were inferior to other agents for preventing mortality and stroke.
CONCLUSIONS: Beta-blockers substantially reduce mortality in HF patients in sinus rhythm, but for other conditions, clinicians need to weigh up both benefit and potential risk.
Landiolol (Onoact(®)) is an intravenously administered, ultra short-acting β1-blocker with an elimination half-life of 3-4 min and ≈8-fold greater cardioselectivity than esmolol in vitro. It is approved in Japan for the treatment of intraoperative and postoperative tachyarrhythmias, but in clinical practice is also used to prevent postoperative tachyarrhythmias, such as atrial fibrillation after coronary artery bypass grafting. Randomized controlled trials in patients undergoing open-heart surgery demonstrated that various dosages of landiolol (0.0005-0.04 mg/kg/min) [0.5-40 μg/kg/min] were more effective than diltiazem in converting postoperative atrial fibrillation to normal sinus rhythm during the first 8 h after surgery, and were more effective than placebo (or no landiolol) in preventing the development of atrial fibrillation during the first week after surgery (primary efficacy endpoints). In patients undergoing surgical procedures, landiolol 0.125 mg/kg/min for 1 min followed by 0.04 mg/kg/min for 10 min was superior to placebo in improving intraoperative tachycardia in randomized double-blind trials. The beneficial effects of landiolol in attenuating adverse haemodynamic or other changes that can occur during surgery or invasive procedures (e.g. percutaneous coronary intervention) have been demonstrated in a large number of randomized controlled trials. For example, several studies showed that landiolol attenuated the increase in heart rate associated with tracheal intubation, without adversely affecting blood pressure or other haemodynamic parameters. Landiolol was generally well tolerated in clinical trials, with a relatively low risk of hypotension and bradycardia, although routine monitoring of cardiac function during landiolol administration is important. In general, adverse events such as reduced blood pressure resolve quickly after discontinuation of landiolol. Thus, as an ultra short-acting β1-blocker with a rapid onset of action and readily titratable and rapidly reversible effects, landiolol represents an important agent for the management of intraoperative and postoperative tachyarrhythmias.
BACKGROUND: The perioperative administration of beta blockers is a controversial issue. Numerous trials failed to show any significant benefit or disadvantage because of low event rates and insufficient statistical power.
METHODS: In July 2005 McGory et al. and Devereaux et al. separately published 2 meta-analyses, raising the question of the perioperative administration of beta blockers for patients undergoing non-cardiac surgery. In February 2006, Schouten et al. published an additional meta-analysis concerning the same question. This evidence is supplemented by the publication of Lindenauer et al. in 2005. These trials will be critically appraised in this review.
RESULTS: McGory et al. concluded from their data that the perioperative administration of beta blockers significantly reduced cardiovascular mortality. However, this conclusion is clearly not valid because of methodological deficits of the meta-analysis. In addition, the publications by Devereaux et al. and Schouten et al. did not support the results of the analysis by McGory et al.
CONCLUSIONS: There is still no clear evidence to prove a significant benefit for the unselected perioperative use of beta blockers in patients undergoing non-cardiac surgery. While high-risk patients and those undergoing major surgical procedures seem to profit, low-risk patients may be more harmed than helped by this intervention. The fact that 3 meta-analyses raising the same question produced substantially different results, underlines the importance of critically appraising each meta-analysis.
Beta-blockers are widely used for many cardiovascular conditions; however, their efficacy in contemporary clinical practice remains uncertain.
METHODS:
We performed a prospectively designed, umbrella review of meta-analyses of randomised controlled trials (RCTs) investigating the evidence of beta-blockers in the contemporary management of coronary artery disease (CAD), heart failure (HF), patients undergoing surgery or hypertension (registration: PROSPERO CRD42016038375). We searched MEDLINE, EMBASE and the Cochrane Library from inception until December 2018. Outcomes were analysed as beta-blockers versus control for all-cause mortality, myocardial infarction (MI), incident HF or stroke. Two independent investigators abstracted the data, assessed the quality of the evidence and rated the certainty of evidence.
RESULTS:
We identified 98 meta-analyses, including 284 unique RCTs and 1,617,523 patient-years of follow-up. In CAD, 12 meta-analyses (93 RCTs, 103,481 patients) showed that beta-blockers reduced mortality in analyses before routine reperfusion, but there was a lack of benefit in contemporary studies where ≥ 50% of patients received thrombolytics or intervention. Beta-blockers reduced incident MI at the expense of increased HF. In HF with reduced ejection fraction, 34 meta-analyses (66 RCTs, 35,383 patients) demonstrated a reduction in mortality and HF hospitalisation with beta-blockers in sinus rhythm, but not in atrial fibrillation. In patients undergoing surgery, 23 meta-analyses (89 RCTs, 19,211 patients) showed no effect of beta-blockers on mortality for cardiac surgery, but increased mortality in non-cardiac surgery. In non-cardiac surgery, beta-blockers reduced MI after surgery but increased the risk of stroke. In hypertension, 27 meta-analyses (36 RCTs, 260,549 patients) identified no benefit versus placebo, but beta-blockers were inferior to other agents for preventing mortality and stroke.
CONCLUSIONS:
Beta-blockers substantially reduce mortality in HF patients in sinus rhythm, but for other conditions, clinicians need to weigh up both benefit and potential risk.
