Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis

Dipak Kotecha; Luis Manzano; Henry Krum; Giuseppe Rosano; Jane Holmes; Douglas G Altman; Peter D Collins; Milton Packer; John Wikstrand; Andrew J S Coats; John G F Cleland; Paulus Kirchhof; Thomas G von Lueder; Alan S Rigby; Bert Andersson; Gregory Yh Lip; Dirk J van Veldhuisen; Marcelo C Shibata; Hans Wedel; Michael Böhm; Marcus D Flather; Beta-Blockers in Heart Failure Collaborative Group

doi:10.1136/bmj.i1855

Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis

Dipak Kotecha, Luis Manzano, Henry Krum, Giuseppe Rosano, Jane Holmes, Douglas G Altman, Peter D Collins, Milton Packer, John Wikstrand, Andrew J S Coats, John G F Cleland, Paulus Kirchhof, Thomas G von Lueder, Alan S Rigby, Bert Andersson, Gregory Yh Lip, Dirk J van Veldhuisen, Marcelo C Shibata, Hans Wedel, Michael BöhmMarcus D Flather, Beta-Blockers in Heart Failure Collaborative Group

Cardiovascular Sciences

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

67 Citations (Scopus)

216 Downloads (Pure)

Abstract

OBJECTIVES: To determine the efficacy and tolerability of β blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials.

DESIGN: Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45.

PARTICIPANTS: 13 833 patients from 11 trials; median age 64; 24% women.

MAIN OUTCOME MEASURES: The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model.

RESULTS: Compared with placebo, β blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by β blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give β blockers, 15.6% in those receiving placebo).

CONCLUSION: Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive β blockers to reduce the risk of death and admission to hospital.Registration PROSPERO CRD42014010012; Clinicaltrials.govNCT00832442.

Original language	English
Article number	i1855
Number of pages	10
Journal	BMJ
Volume	353
DOIs	https://doi.org/10.1136/bmj.i1855
Publication status	Published - 20 Apr 2016

Access to Document

10.1136/bmj.i1855Licence: Creative Commons: Attribution-NonCommercial (CC BY-NC)

KotechaD2016EffectFinal published version, 606 KBLicence: Creative Commons: Attribution (CC BY)

Cite this

Kotecha, D., Manzano, L., Krum, H., Rosano, G., Holmes, J., Altman, D. G., Collins, P. D., Packer, M., Wikstrand, J., Coats, A. J. S., Cleland, J. G. F., Kirchhof, P., von Lueder, T. G., Rigby, A. S., Andersson, B., Lip, G. Y., van Veldhuisen, D. J., Shibata, M. C., Wedel, H., ... Beta-Blockers in Heart Failure Collaborative Group (2016). Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis. BMJ, 353, Article i1855. https://doi.org/10.1136/bmj.i1855

@article{0170dde31411431c95cce1010fc652e4,

title = "Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis",

abstract = "OBJECTIVES: To determine the efficacy and tolerability of β blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials.DESIGN: Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45.PARTICIPANTS: 13 833 patients from 11 trials; median age 64; 24% women.MAIN OUTCOME MEASURES: The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model.RESULTS: Compared with placebo, β blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by β blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give β blockers, 15.6% in those receiving placebo).CONCLUSION: Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive β blockers to reduce the risk of death and admission to hospital.Registration PROSPERO CRD42014010012; Clinicaltrials.govNCT00832442.",

author = "Dipak Kotecha and Luis Manzano and Henry Krum and Giuseppe Rosano and Jane Holmes and Altman, {Douglas G} and Collins, {Peter D} and Milton Packer and John Wikstrand and Coats, {Andrew J S} and Cleland, {John G F} and Paulus Kirchhof and {von Lueder}, {Thomas G} and Rigby, {Alan S} and Bert Andersson and Lip, {Gregory Yh} and {van Veldhuisen}, {Dirk J} and Shibata, {Marcelo C} and Hans Wedel and Michael B{\"o}hm and Flather, {Marcus D} and {Beta-Blockers in Heart Failure Collaborative Group}",

note = "Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.",

year = "2016",

month = apr,

day = "20",

doi = "10.1136/bmj.i1855",

language = "English",

volume = "353",

journal = "BMJ",

issn = "0959-535X",

publisher = "BMJ Publishing Group",

}

Kotecha, D, Manzano, L, Krum, H, Rosano, G, Holmes, J, Altman, DG, Collins, PD, Packer, M, Wikstrand, J, Coats, AJS, Cleland, JGF, Kirchhof, P, von Lueder, TG, Rigby, AS, Andersson, B, Lip, GY, van Veldhuisen, DJ, Shibata, MC, Wedel, H, Böhm, M, Flather, MD & Beta-Blockers in Heart Failure Collaborative Group 2016, 'Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis', BMJ, vol. 353, i1855. https://doi.org/10.1136/bmj.i1855

TY - JOUR

T1 - Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction

T2 - individual patient data meta-analysis

AU - Kotecha, Dipak

AU - Manzano, Luis

AU - Krum, Henry

AU - Rosano, Giuseppe

AU - Holmes, Jane

AU - Altman, Douglas G

AU - Collins, Peter D

AU - Packer, Milton

AU - Wikstrand, John

AU - Coats, Andrew J S

AU - Cleland, John G F

AU - Kirchhof, Paulus

AU - von Lueder, Thomas G

AU - Rigby, Alan S

AU - Andersson, Bert

AU - Lip, Gregory Yh

AU - van Veldhuisen, Dirk J

AU - Shibata, Marcelo C

AU - Wedel, Hans

AU - Böhm, Michael

AU - Flather, Marcus D

AU - Beta-Blockers in Heart Failure Collaborative Group

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PY - 2016/4/20

Y1 - 2016/4/20

N2 - OBJECTIVES: To determine the efficacy and tolerability of β blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials.DESIGN: Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45.PARTICIPANTS: 13 833 patients from 11 trials; median age 64; 24% women.MAIN OUTCOME MEASURES: The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model.RESULTS: Compared with placebo, β blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by β blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give β blockers, 15.6% in those receiving placebo).CONCLUSION: Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive β blockers to reduce the risk of death and admission to hospital.Registration PROSPERO CRD42014010012; Clinicaltrials.govNCT00832442.

AB - OBJECTIVES: To determine the efficacy and tolerability of β blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials.DESIGN: Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45.PARTICIPANTS: 13 833 patients from 11 trials; median age 64; 24% women.MAIN OUTCOME MEASURES: The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model.RESULTS: Compared with placebo, β blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by β blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give β blockers, 15.6% in those receiving placebo).CONCLUSION: Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive β blockers to reduce the risk of death and admission to hospital.Registration PROSPERO CRD42014010012; Clinicaltrials.govNCT00832442.

U2 - 10.1136/bmj.i1855

DO - 10.1136/bmj.i1855

M3 - Article

C2 - 27098105

SN - 0959-535X

VL - 353

JO - BMJ

JF - BMJ

M1 - i1855

ER -

Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis

Abstract

Access to Document

Fingerprint

Cite this