Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis
Open accessAbstract
Background Atrial fibrillation and heart failure often coexist, causing substantial cardiovascular morbidity and mortality. β blockers are indicated in patients with symptomatic heart failure with reduced ejection fraction; however, the efficacy of these drugs in patients with concomitant atrial fibrillation is uncertain. We therefore meta-analysed individual-patient data to assess the efficacy of β blockers in patients with heart failure and sinus rhythm compared with atrial fibrillation.Methods We extracted individual-patient data from ten randomised controlled trials of the comparison of β blockers versus placebo in heart failure. The presence of sinus rhythm or atrial fibrillation was ascertained from the baseline electrocardiograph. The primary outcome was all-cause mortality. Analysis was by intention to treat. Outcome data were meta-analysed with an adjusted Cox proportional hazards regression. The study is registered with Clinicaltrials.gov, number NCT0083244, and PROSPERO, number CRD42014010012.Findings 18,254 patients were assessed, and of these 13,946 (76%) had sinus rhythm and 3066 (17%) had atrial fibrillation at baseline. Crude death rates over a mean follow-up of 1·5 years (SD 1·1) were 16% (2237 of 13,945) in patients with sinus rhythm and 21% (633 of 3064) in patients with atrial fibrillation. β-blocker therapy led to a significant reduction in all-cause mortality in patients with sinus rhythm (hazard ratio 0·73, 0·67-0·80; p<0·001), but not in patients with atrial fibrillation (0·97, 0·83-1·14; p=0·73), with a significant p value for interaction of baseline rhythm (p=0·002). The lack of efficacy for the primary outcome was noted in all subgroups of atrial fibrillation, including age, sex, left ventricular ejection fraction, New York Heart Association class, heart rate, and baseline medical therapy.Interpretation Based on our findings, β blockers should not be used preferentially over other rate-control medications and not regarded as standard therapy to improve prognosis in patients with concomitant heart failure and atrial fibrillation.Funding Menarini Farmaceutica Internazionale (administrative support grant).
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Between 10% and 40% of AF patients are hospitalized each year.
“between 10% and 40% of AF patients are hospitalized each year.23,34,35”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [23]
A meta-analysis using individual patient data from randomized controlled trials found no reduction in mortality from beta-blockers versus placebo in those with AF at baseline (HR 0.97, 95% CI 0.83-1.14).
“although a meta-analysis using individual patient data from randomized controlled trials (RCTs) found no reduction in mortality from beta-blockers versus placebo in those with AF at baseline (HR 0.97, 95% CI 0.83-1.14).”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [23]
Beta-blocker therapy was associated with a 33% reduction in the adjusted odds of incident AF in HFrEF patients pretreated with ACE inhibitors/ARBs.
“Beta-blocker therapy was associated with a 33% reduction in the adjusted odds of incident AF in HFrEF patients pretreated with ACE inhibitors/ARBs”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [23]
In HFrEF patients, the prognostic benefit of beta-blockers seen in sinus rhythm is lost in those with AF.
“Interestingly, the prognostic benefit of beta-blockers seen in HFrEF patients with sinus rhythm is lost in those with AF.”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [23]
In the same meta-analysis, there was a clear benefit of beta-blockers on all-cause mortality in patients with sinus rhythm (HR 0.73; 95% CI 0.67-0.80; P < 0.001).
“In an individual patient-level meta-analysis of RCTs, beta-blockers did not reduce all-cause mortality compared to placebo in those with AF at baseline (HR 0.97; 95% CI 0.83-1.14;P = 0.73), whereas there was a clear benefit in patients with sinus rhythm (HR 0.73; 95% CI 0.67-0.80;P < 0.001).23”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [23]
In an individual patient-level meta-analysis of RCTs, beta-blockers did not reduce all-cause mortality compared to placebo in those with AF at baseline (HR 0.97; 95% CI 0.83-1.14; P = 0.73).
“In an individual patient-level meta-analysis of RCTs, beta-blockers did not reduce all-cause mortality compared to placebo in those with AF at baseline (HR 0.97; 95% CI 0.83-1.14;P = 0.73), whereas there was a clear benefit in patients with sinus rhythm (HR 0.73; 95% CI 0.67-0.80;P < 0.001).23”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [23]
The meta-analysis included 3066 participants with HFrEF and AF, showed consistency across all subgroups and outcomes, with no heterogeneity between the 10 RCTs included (I2 = 0%).
“The study, which included 3066 participants with HFrEF and AF, showed consistency across all subgroups and outcomes, with no heterogeneity between the 10 RCTs included (I 2 = 0%).”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [23]
Beta-blockers are associated with a reduced risk of new-onset atrial fibrillation compared with placebo in patients with reduced ejection fraction and sinus rhythm.
“Compared with placebo, beta-blockers are associated with a reduced risk of new-onset AF in patients with reduced ejection fraction and sinus rhythm.23”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [23]
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- Authors
- Kotecha, D., Holmes, J., Krum, H., Altman, D. G., Manzano, L., Cleland, J. G. F., Lip, G. Y. H., Coats, A. J. S., Andersson, B., Kirchhof, P., von Lueder, T. G., Wedel, H., Rosano, G., Shibata, M. C., Rigby, A., & Flather, M. D.
- Affiliations
- Royal Brompton & Harefield NHS Foundation Trust (GB)
- University of Oxford (GB)
- Monash University (AU)
- University of Hull (GB)
- Sandwell & West Birmingham Hospitals NHS Trust (GB)
- University of Warwick (GB)
- Sahlgrenska University Hospital (SE)
- Nordic School of Public Health (SE)
- IRCCS San Raffaele Roma (IT)
- University of Alberta (CA)
- Castle Hill Hospital (GB)
- University of East Anglia (GB)
- Corresponding author
- Kotecha, Dipak
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 384
- Issue
- 9961
- Pages
- 2235-2243
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2154650976
- Cited by
- 579
- References
- 54
- Citations by year
- 2026: 31 · 2025: 35 · 2024: 34 · 2023: 44 · 2022: 50 · 2021: 68 · 2020: 50 · 2019: 49 · 2018: 44 · 2017: 59 · 2016: 55 · 2015: 51 · 2014: 7
- FWCI
- 9.24
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by-nc-nd)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- National Institute for Health and Care Research (CL-2012-09-001, NF-SI-0611-10227)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Keywords
- beta-blockers, heart failure, atrial fibrillation, all-cause mortality, sinus rhythm, heart failure with reduced ejection fraction, rate control, subgroup interaction, cardiovascular prognosis, NYHA functional class, left ventricular ejection fraction, heart failure with preserved ejection fraction
- MeSH terms
- Adrenergic beta-Antagonists, Atrial Fibrillation, Electrocardiography, Heart Failure, Humans, Length of Stay, Patient Admission, Randomized Controlled Trials as Topic, Stroke
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