Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis

Dipak Kotecha; Jane Holmes; Henry Krum; Douglas G Altman; Luis Manzano; John G F Cleland; Gregory Y H Lip; Andrew J S Coats; Bert Andersson; Paulus Kirchhof; Thomas G Von Lueder; Hans Wedel; Giuseppe Rosano; Marcelo C Shibata; Alan Rigby; Marcus D Flather

doi:10.1016/S0140-6736(14)61373-8

Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis

Dipak Kotecha, Jane Holmes, Henry Krum, Douglas G Altman, Luis Manzano, John G F Cleland, Gregory Y H Lip, Andrew J S Coats, Bert Andersson, Paulus Kirchhof, Thomas G Von Lueder, Hans Wedel, Giuseppe Rosano, Marcelo C Shibata, Alan Rigby, Marcus D Flather

Research output: Contribution to journal › Article › peer-review

468 Citations (SciVal)

Abstract

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.

Original language	English
Pages (from-to)	2235-2243
Number of pages	9
Journal	The Lancet
Volume	384
Issue number	9961
Early online date	2 Sep 2014
DOIs	https://doi.org/10.1016/S0140-6736(14)61373-8
Publication status	Published - 20 Dec 2014

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10.1016/S0140-6736(14)61373-8

Marcus Flather
- M.Flatheruea.acuk
- Norwich Medical School - Emeritus Professor
- Cardiovascular and Metabolic Health - Member
Person: Honorary, Research Group Member

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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. (2014). Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis. The Lancet, 384(9961), 2235-2243. https://doi.org/10.1016/S0140-6736(14)61373-8

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title = "Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis",

abstract = "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.",

author = "Dipak Kotecha and Jane Holmes and Henry Krum and Altman, {Douglas G} and Luis Manzano and Cleland, {John G F} and Lip, {Gregory Y H} and Coats, {Andrew J S} and Bert Andersson and Paulus Kirchhof and {Von Lueder}, {Thomas G} and Hans Wedel and Giuseppe Rosano and Shibata, {Marcelo C} and Alan Rigby and Flather, {Marcus D}",

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language = "English",

volume = "384",

pages = "2235--2243",

journal = "The Lancet",

issn = "0140-6736",

publisher = "Elsevier",

number = "9961",

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Kotecha, D, Holmes, J, Krum, H, Altman, DG, Manzano, L, Cleland, JGF, Lip, GYH, Coats, AJS, Andersson, B, Kirchhof, P, Von Lueder, TG, Wedel, H, Rosano, G, Shibata, MC, Rigby, A & Flather, MD 2014, 'Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis', The Lancet, vol. 384, no. 9961, pp. 2235-2243. https://doi.org/10.1016/S0140-6736(14)61373-8

TY - JOUR

T1 - Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis

AU - Kotecha, Dipak

AU - Holmes, Jane

AU - Krum, Henry

AU - Altman, Douglas G

AU - Manzano, Luis

AU - Cleland, John G F

AU - Lip, Gregory Y H

AU - Coats, Andrew J S

AU - Andersson, Bert

AU - Kirchhof, Paulus

AU - Von Lueder, Thomas G

AU - Wedel, Hans

AU - Rosano, Giuseppe

AU - Shibata, Marcelo C

AU - Rigby, Alan

AU - Flather, Marcus D

PY - 2014/12/20

Y1 - 2014/12/20

N2 - 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.

AB - 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.

U2 - 10.1016/S0140-6736(14)61373-8

DO - 10.1016/S0140-6736(14)61373-8

M3 - Article

VL - 384

SP - 2235

EP - 2243

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9961

ER -

Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis

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Marcus Flather

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