Efficacy and safety of intravenous beta-blockers in acute atrial fibrillation and flutter is dependent on beta-1 selectivity: A systematic review and meta-analysis of randomised trials

Madeleine  Perrett; Nisha Gohil; Otilia Tica; Karina Bunting; Dipak Kotecha

doi:10.1007/s00392-023-02295-0

Efficacy and safety of intravenous beta-blockers in acute atrial fibrillation and flutter is dependent on beta-1 selectivity: A systematic review and meta-analysis of randomised trials

Madeleine Perrett, Nisha Gohil, Otilia Tica, Karina Bunting, Dipak Kotecha^*

^*Corresponding author for this work

Cardiovascular Sciences

Research output: Contribution to journal › Review article › peer-review

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Abstract

Background: Intravenous beta-blockers are commonly used to manage patients with acute atrial fibrillation (AF) and atrial flutter (AFl), but the choice of specific agent is often not evidence-based.

Methods: A prospectively-registered systematic review and meta-analysis of randomised trials (PROSPERO: CRD42020204772) to compare the safety and efficacy of intravenous beta-blockers against alternative pharmacological agents.

Results: Twelve trials comparing beta-blockers with diltiazem, digoxin, verapamil, anti-arrhythmic drugs and placebo were included, with variable risk of bias and 1152 participants. With high heterogeneity (I² = 87%; p < 0.001), there was no difference in the primary outcomes of heart rate reduction (standardised mean difference − 0.65 beats/minute compared to control, 95% CI − 1.63 to 0.32; p = 0.19) or the proportion that achieved target heart rate (risk ratio [RR] 0.85, 95% CI 0.36–1.97; p = 0.70). Conventional selective beta-1 blockers were inferior for target heart rate reduction versus control (RR 0.33, 0.17–0.64; p < 0.001), whereas super-selective beta-1 blockers were superior (RR 1.98, 1.54–2.54; p < 0.001). There was no significant difference between beta-blockers and comparators for secondary outcomes of conversion to sinus rhythm (RR
1.15, 0.90–1.46; p = 0.28), hypotension (RR 1.85, 0.87–3.93; p = 0.11), bradycardia (RR 1.29, 0.25–6.82; p = 0.76) or adverse events leading to drug discontinuation (RR 1.03, 0.49–2.17; p = 0.93). The incidence of hypotension and bradycardia were greater with non-selective beta-blockers (p = 0.031 and p < 0.001).

Conclusions: Across all intravenous beta-blockers, there was no difference with other medications for acute heart rate control in atrial fibrillation and flutter. Efficacy and safety may be improved by choosing beta-blockers with higher beta-1 selectivity.

Original language	English
Journal	Clinical Research in Cardiology
Early online date	1 Sept 2023
DOIs	https://doi.org/10.1007/s00392-023-02295-0
Publication status	E-pub ahead of print - 1 Sept 2023

Bibliographical note

Funding:
This is an independent systematic review commissioned by Amomed (now part of the AOP Orphan Group). The commissioning company had no role in any aspect of the study design, review process, analysis or manuscript preparation. Project staff were funded by grants from the: British Heart Foundation Career Development Research Fellowship (FS/CDRF/21/21032), MRC Health Data Research UK (HDRUK/CFC/01), the EU/EEPIA Innovative Medicines Initiative (BigData@Heart 116074), National Institute for Health Research Birmingham Biomedical Research Centre (NIHR203326), UK National Health Service -Data for R&D- Subnational Secure Data Environment programme West Midlands, and the British Heart Foundation Accelerator to the University of Birmingham (AA/18/2/34218). The opinions expressed in this paper are those of the authors and do not represent any of the listed organizations.

Keywords

Atrial fibrillation
Atrial flutter
Beta-blockers
Acute
Systematic review
Meta-analysis

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10.1007/s00392-023-02295-0Licence: Creative Commons: Attribution (CC BY)

PerrettM2023EfficacyFinal published version, 1.19 MBLicence: Creative Commons: Attribution (CC BY)

1 Finished
1 Active

Improving the assessment of heart function in patients with atrial fibrillation (INDEX-AF)
Bunting, K.
British Heart Foundation
1/01/22 → 30/09/26
Project: Research
H2020_COLLAB(IMI-JU)_BIGDATA@HEART
Kotecha, D. & Kirchhof, P.
European Commission
1/03/17 → 28/02/23
Project: Research

Cite this

@article{b2437fc2960b43d488fde1708d4a4dcd,

title = "Efficacy and safety of intravenous beta-blockers in acute atrial fibrillation and flutter is dependent on beta-1 selectivity: A systematic review and meta-analysis of randomised trials",

abstract = "Background: Intravenous beta-blockers are commonly used to manage patients with acute atrial fibrillation (AF) and atrial flutter (AFl), but the choice of specific agent is often not evidence-based.Methods: A prospectively-registered systematic review and meta-analysis of randomised trials (PROSPERO: CRD42020204772) to compare the safety and efficacy of intravenous beta-blockers against alternative pharmacological agents.Results: Twelve trials comparing beta-blockers with diltiazem, digoxin, verapamil, anti-arrhythmic drugs and placebo were included, with variable risk of bias and 1152 participants. With high heterogeneity (I2 = 87%; p < 0.001), there was no difference in the primary outcomes of heart rate reduction (standardised mean difference − 0.65 beats/minute compared to control, 95% CI − 1.63 to 0.32; p = 0.19) or the proportion that achieved target heart rate (risk ratio [RR] 0.85, 95% CI 0.36–1.97; p = 0.70). Conventional selective beta-1 blockers were inferior for target heart rate reduction versus control (RR 0.33, 0.17–0.64; p < 0.001), whereas super-selective beta-1 blockers were superior (RR 1.98, 1.54–2.54; p < 0.001). There was no significant difference between beta-blockers and comparators for secondary outcomes of conversion to sinus rhythm (RR 1.15, 0.90–1.46; p = 0.28), hypotension (RR 1.85, 0.87–3.93; p = 0.11), bradycardia (RR 1.29, 0.25–6.82; p = 0.76) or adverse events leading to drug discontinuation (RR 1.03, 0.49–2.17; p = 0.93). The incidence of hypotension and bradycardia were greater with non-selective beta-blockers (p = 0.031 and p < 0.001).Conclusions: Across all intravenous beta-blockers, there was no difference with other medications for acute heart rate control in atrial fibrillation and flutter. Efficacy and safety may be improved by choosing beta-blockers with higher beta-1 selectivity.",

keywords = "Atrial fibrillation, Atrial flutter, Beta-blockers, Acute, Systematic review, Meta-analysis",

author = "Madeleine Perrett and Nisha Gohil and Otilia Tica and Karina Bunting and Dipak Kotecha",

note = "Funding: This is an independent systematic review commissioned by Amomed (now part of the AOP Orphan Group). The commissioning company had no role in any aspect of the study design, review process, analysis or manuscript preparation. Project staff were funded by grants from the: British Heart Foundation Career Development Research Fellowship (FS/CDRF/21/21032), MRC Health Data Research UK (HDRUK/CFC/01), the EU/EEPIA Innovative Medicines Initiative (BigData@Heart 116074), National Institute for Health Research Birmingham Biomedical Research Centre (NIHR203326), UK National Health Service -Data for R&D- Subnational Secure Data Environment programme West Midlands, and the British Heart Foundation Accelerator to the University of Birmingham (AA/18/2/34218). The opinions expressed in this paper are those of the authors and do not represent any of the listed organizations.",

year = "2023",

month = sep,

day = "1",

doi = "10.1007/s00392-023-02295-0",

language = "English",

journal = "Clinical Research in Cardiology",

issn = "1861-0684",

publisher = "Springer",

}

TY - JOUR

T1 - Efficacy and safety of intravenous beta-blockers in acute atrial fibrillation and flutter is dependent on beta-1 selectivity

T2 - A systematic review and meta-analysis of randomised trials

AU - Perrett, Madeleine

AU - Gohil, Nisha

AU - Tica, Otilia

AU - Bunting, Karina

AU - Kotecha, Dipak

N1 - Funding: This is an independent systematic review commissioned by Amomed (now part of the AOP Orphan Group). The commissioning company had no role in any aspect of the study design, review process, analysis or manuscript preparation. Project staff were funded by grants from the: British Heart Foundation Career Development Research Fellowship (FS/CDRF/21/21032), MRC Health Data Research UK (HDRUK/CFC/01), the EU/EEPIA Innovative Medicines Initiative (BigData@Heart 116074), National Institute for Health Research Birmingham Biomedical Research Centre (NIHR203326), UK National Health Service -Data for R&D- Subnational Secure Data Environment programme West Midlands, and the British Heart Foundation Accelerator to the University of Birmingham (AA/18/2/34218). The opinions expressed in this paper are those of the authors and do not represent any of the listed organizations.

PY - 2023/9/1

Y1 - 2023/9/1

N2 - Background: Intravenous beta-blockers are commonly used to manage patients with acute atrial fibrillation (AF) and atrial flutter (AFl), but the choice of specific agent is often not evidence-based.Methods: A prospectively-registered systematic review and meta-analysis of randomised trials (PROSPERO: CRD42020204772) to compare the safety and efficacy of intravenous beta-blockers against alternative pharmacological agents.Results: Twelve trials comparing beta-blockers with diltiazem, digoxin, verapamil, anti-arrhythmic drugs and placebo were included, with variable risk of bias and 1152 participants. With high heterogeneity (I2 = 87%; p < 0.001), there was no difference in the primary outcomes of heart rate reduction (standardised mean difference − 0.65 beats/minute compared to control, 95% CI − 1.63 to 0.32; p = 0.19) or the proportion that achieved target heart rate (risk ratio [RR] 0.85, 95% CI 0.36–1.97; p = 0.70). Conventional selective beta-1 blockers were inferior for target heart rate reduction versus control (RR 0.33, 0.17–0.64; p < 0.001), whereas super-selective beta-1 blockers were superior (RR 1.98, 1.54–2.54; p < 0.001). There was no significant difference between beta-blockers and comparators for secondary outcomes of conversion to sinus rhythm (RR 1.15, 0.90–1.46; p = 0.28), hypotension (RR 1.85, 0.87–3.93; p = 0.11), bradycardia (RR 1.29, 0.25–6.82; p = 0.76) or adverse events leading to drug discontinuation (RR 1.03, 0.49–2.17; p = 0.93). The incidence of hypotension and bradycardia were greater with non-selective beta-blockers (p = 0.031 and p < 0.001).Conclusions: Across all intravenous beta-blockers, there was no difference with other medications for acute heart rate control in atrial fibrillation and flutter. Efficacy and safety may be improved by choosing beta-blockers with higher beta-1 selectivity.

AB - Background: Intravenous beta-blockers are commonly used to manage patients with acute atrial fibrillation (AF) and atrial flutter (AFl), but the choice of specific agent is often not evidence-based.Methods: A prospectively-registered systematic review and meta-analysis of randomised trials (PROSPERO: CRD42020204772) to compare the safety and efficacy of intravenous beta-blockers against alternative pharmacological agents.Results: Twelve trials comparing beta-blockers with diltiazem, digoxin, verapamil, anti-arrhythmic drugs and placebo were included, with variable risk of bias and 1152 participants. With high heterogeneity (I2 = 87%; p < 0.001), there was no difference in the primary outcomes of heart rate reduction (standardised mean difference − 0.65 beats/minute compared to control, 95% CI − 1.63 to 0.32; p = 0.19) or the proportion that achieved target heart rate (risk ratio [RR] 0.85, 95% CI 0.36–1.97; p = 0.70). Conventional selective beta-1 blockers were inferior for target heart rate reduction versus control (RR 0.33, 0.17–0.64; p < 0.001), whereas super-selective beta-1 blockers were superior (RR 1.98, 1.54–2.54; p < 0.001). There was no significant difference between beta-blockers and comparators for secondary outcomes of conversion to sinus rhythm (RR 1.15, 0.90–1.46; p = 0.28), hypotension (RR 1.85, 0.87–3.93; p = 0.11), bradycardia (RR 1.29, 0.25–6.82; p = 0.76) or adverse events leading to drug discontinuation (RR 1.03, 0.49–2.17; p = 0.93). The incidence of hypotension and bradycardia were greater with non-selective beta-blockers (p = 0.031 and p < 0.001).Conclusions: Across all intravenous beta-blockers, there was no difference with other medications for acute heart rate control in atrial fibrillation and flutter. Efficacy and safety may be improved by choosing beta-blockers with higher beta-1 selectivity.

KW - Atrial fibrillation

KW - Atrial flutter

KW - Beta-blockers

KW - Acute

KW - Systematic review

KW - Meta-analysis

U2 - 10.1007/s00392-023-02295-0

DO - 10.1007/s00392-023-02295-0

M3 - Review article

C2 - 37658166

SN - 1861-0684

JO - Clinical Research in Cardiology

JF - Clinical Research in Cardiology

ER -

Efficacy and safety of intravenous beta-blockers in acute atrial fibrillation and flutter is dependent on beta-1 selectivity: A systematic review and meta-analysis of randomised trials

Abstract

Bibliographical note

Keywords

Access to Document

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Projects

Improving the assessment of heart function in patients with atrial fibrillation (INDEX-AF)

H2020_COLLAB(IMI-JU)_BIGDATA@HEART

Cite this