Evidence map›Paper›PMID 27098105›Full record

SynthesisBMJ (Clinical research ed.)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.

Dipak Kotecha, Luis Manzano, Henry Krum, Giuseppe Rosano, Jane Holmes, Douglas G Altman, Peter D Collins, Milton Packer, John Wikstrand, Andrew J S Coats and 12 more

Registry-linked trialOpen access · hybridAbstract readMeta-AnalysisReview
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMJ (Clinical research ed.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00832442 (Collaborative Systematic Overview of Randomised Controlled Trials of Beta-Blockers in the Treatment of Heart Failure), which is not on this map. Cited by 61 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 6 pooled it
12.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00832442 unknown statusnot on this map

Collaborative Systematic Overview of Randomised Controlled Trials of Beta-Blockers in the Treatment of Heart Failure

TypeobservationalSponsorRoyal Brompton & Harefield NHS Foundation TrustRan2008 to 2012Enrolled18,240ConditionsHeart FailureArmsBeta blocker, Placebo
3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 6 syntheses or guidelines pooled it, 136 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Trial
  8. Trial
  9. Trial
  10. Article
  11. Article
  12. Review
  13. Article
  14. Heart Failure in Older Patients: An Update.Journal of clinical medicine · 2025
    Review
  15. Assessing the application of American Heart Association (AHA) guidelines in the management of heart failure with reduced ejection fraction.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2025
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Protective effects of GαNaunyn-Schmiedeberg's archives of pharmacology · 2024
    Article

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 17 institutions in 10 countries.

Dipak KotechaUniversity of Birmingham Institute of Cardiovascular Sciences, Birmingham, UK Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, Australia d.kotecha@bham.ac.uk.
Luis ManzanoInternal Medicine Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain.
Henry KrumCentre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, Australia.
Giuseppe RosanoDepartment of Medical Sciences, IRCCS San Raffaele Pisana, Roma, Italy Cardiovascular and Cell Science Institute, St George's University of London, London, UK.
Jane HolmesCentre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Douglas G AltmanCentre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Peter D CollinsNational Heart and Lung Institute, Imperial College, London, UK.
Milton PackerBaylor University Medical Center, Dallas, USA.
John WikstrandWallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
Andrew J S CoatsMonash Warwick Alliance, Monash University, Melbourne, Australia Monash Warwick Alliance, University of Warwick, Warwick, UK.
John G F ClelandNational Heart and Lung Institute, Imperial College, London, UK.
Paulus KirchhofUniversity of Birmingham Institute of Cardiovascular Sciences, Birmingham, UK.
Thomas G von LuederDepartment of Cardiology, Oslo University Hospital, Oslo, Norway.
Alan S RigbyAcademic Cardiology, Castle Hill Hospital, Kingston upon Hull, UK.
Bert AnderssonWallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
Gregory Y H LipUniversity of Birmingham Institute of Cardiovascular Sciences, Birmingham, UK.
Dirk J van VeldhuisenDepartment of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands.
Marcelo C ShibataDivision of Cardiology, University of Alberta, Edmonton, Canada.
Hans WedelNordic School of Public Health, Gothenburg, Sweden.
Michael BöhmUniversitätsklinikum des Saarlandes, Homburg/Saar, Germany.
Marcus D FlatherNorwich Medical School, University of East Anglia, Norwich, UK.
Beta-Blockers in Heart Failure Collaborative Group
Imperial College London · GBMonash University · AUUniversity of Birmingham · GBUniversity of Gothenburg · SEBaylor University Medical Center · USHospital Universitario Ramón y Cajal · ESIstituto di Ricovero e Cura a Carattere Scientifico San RaffaeleKing's College Hospital · GBNordic School of Public Health · SENuffield Orthopaedic Centre · GBOslo University Hospital · NOUniversitätsklinikum des Saarlandes · DEUniversity Medical Center Groningen · NLUniversity of Alberta · CAUniversity of East Anglia · GBUniversity of Oxford · GBUniversity of Warwick · GB

Funding

British Heart Foundation FS/13/43/30324Department of Health CDF-2015-08-074
6 · The paper itself

Abstract

objectivesTo 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.

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

participants13,833 patients from 11 trials; median age 64; 24% women.

main outcome measuresThe 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.

resultsCompared 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).

conclusionIrrespective 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.gov NCT00832442.

Indexed as

Adrenergic beta-AntagonistsAdultAgedAged, 80 and overAge FactorsFemaleHeart FailureHumansMaleMiddle AgedSex FactorsStroke VolumeTreatment OutcomeAdrenergic beta-Antagonists

Identifiers

PMID27098105
PMCPMC4849174
OpenAlexW2340145920

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.