Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2020 May 5;18(1):103.
doi: 10.1186/s12916-020-01564-3.

Beta-blocker efficacy across different cardiovascular indications: an umbrella review and meta-analytic assessment

Oliver J Ziff  1   2 , Monica Samra  2 , James P Howard  3 , Daniel I Bromage  2   4 , Frank Ruschitzka  5 , Darrel P Francis  3 , Dipak Kotecha  6   7   8
Affiliations
Meta-Analysis

Beta-blocker efficacy across different cardiovascular indications: an umbrella review and meta-analytic assessment

Oliver J Ziff et al. BMC Med. .

Abstract

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.

Keywords: Coronary artery disease; Heart failure; Hypertension; Meta-analysis; Mortality; Myocardial infarction; Perioperative; Stroke; Systematic review.

PubMed Disclaimer

Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form and declare the following: OJZ, MS, JPH, DIB and DPF have no relevant conflicts. FR received as direct personal payment speaker fees, honoraria, consultancy, advisory board fees, investigator, committee member from Amgen, Boehringer Ingelheim Novartis, Pfizer, BMS, Servier, Sanofi Aventis, Zoll Medical, St. Jude Medical, Fresenius Nutrition, Vifor International, Cardiorentis and Heartware and as payment to institution speaker fees, honoraria, consultancy, advisory board fees, investigator, committee member from Bayer, Novartis and St. Jude Medical. DK reports grants from Menarini and personal fees from Bayer, Atricure, Myokardia and Amomed, all outside the submitted work, and is the Chief Investigator of the RATE-AF clinical trial (NCT02391337), Steering Group Lead for the Beta-Blockers in Heart Failure Collaborative Group (BB-meta-HF; NCT NCT00832442), and a member of the consortium for an EU/EFPIA Innovative Medicines Initiative on big data for ACS/AF/HF (116074; BigData@Heart).

Figures

Fig. 1
Fig. 1
Representative coronary artery disease meta-analyses.Most up-to-date and highest quality meta-analyses for coronary artery disease. No individual patient data meta-analyses were available. Trials with routine reperfusion had ≥ 50% of patients receiving thrombolytics or intervention. See Supplemental Figures 3 for full details. IHD, ischaemic heart disease
Fig. 2
Fig. 2
Representative heart failure meta-analyses for all-cause mortality.Most up-to-date and highest quality meta-analyses for heart failure. Results for other outcomes were similar to all-cause mortality. See Supplemental Figure 4 for full details. ACEi, angiotensin-converting enzyme inhibitors; ARB, angiotensin receptor blockers; bpm, beats/min; CKD, chronic kidney disease; HR, heart rate; LVEF, left ventricular ejection fraction
Fig. 3
Fig. 3
Representative perioperative meta-analyses.Highest quality meta-analyses of perioperative risk reduction using beta-blockers. No individual patient data meta-analyses were available. See Supplemental Figure 5 for full details. The Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) trials II–VI were considered high risk of bias
Fig. 4
Fig. 4
Representative hypertension meta-analyses.Highest quality meta-analyses of hypertension using beta-blockers. No individual patient data meta-analyses were available. See Supplemental Figure 6 for full details. RAS, renin-angiotensin system; TIA, transient ischaemic attack
Fig. 5
Fig. 5
Overview of the evidence base for beta-blockers versus control in cardiovascular health.a Compared to other medications. b In trials with a low risk of bias. c In contemporary trials with majority undergoing reperfusion. AF, atrial fibrillation; CAD, coronary artery disease; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; MI, myocardial infarction; RR, risk ratio
See this image and copyright information in PMC

References

    1. Kotecha D, Manzano L, Krum H, Rosano G, Holmes J, Altman DG, Collins PD, Packer M, Wikstrand J, Coats AJ, et al. Effect of age and sex on efficacy and tolerability of beta blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis. BMJ. 2016;353:i1855. doi: 10.1136/bmj.i1855. - DOI - PMC - PubMed
    1. Barron AJ, Zaman N, Cole GD, Wensel R, Okonko DO, Francis DP. Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control: recommendations for patient information. Int J Cardiol. 2013;168(4):3572–3579. doi: 10.1016/j.ijcard.2013.05.068. - DOI - PMC - PubMed
    1. Hjalmarson A, Elmfeldt D, Herlitz J, Holmberg S, Malek I, Nyberg G, Ryden L, Swedberg K, Vedin A, Waagstein F, et al. Effect on mortality of metoprolol in acute myocardial infarction. A double-blind randomised trial. Lancet. 1981;2(8251):823–827. doi: 10.1016/S0140-6736(81)91101-6. - DOI - PubMed
    1. Chen J, Radford MJ, Wang Y, Marciniak TA, Krumholz HM. Effectiveness of beta-blocker therapy after acute myocardial infarction in elderly patients with chronic obstructive pulmonary disease or asthma. J Am Coll Cardiol. 2001;37(7):1950–1956. doi: 10.1016/S0735-1097(01)01225-6. - DOI - PubMed
    1. O’Gara PT, Kushner FG, Ascheim DD, Casey DE, Jr, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(4):529–555. doi: 10.1161/CIR.0b013e3182742c84. - DOI - PubMed

Publication types

MeSH terms

Substances