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

NCT00832442 | Unknown DMC

• 1 other identifier: CTEU08/d5/BBHF
• Study Type: observational
• Target: 18,240
• Locations: 1 country
• Sites: 2

Brief Summary

Several large trials have shown that beta-blocker treatment reduces the risk of death and hospital admission in patients with symptomatic heart failure. Unfortunately, survey data suggests relatively poor utilisation of beta-blockers, despite ample evidence for good tolerability. Additionally there are several important unanswered questions, such as clinical efficacy for specific sub-populations (women, the elderly and patients with diabetes or other co-morbidities) and the effect of beta-blockers in combination with other medications. Previous meta-analyses, based on published tabular data, have been conducted although this approach has important biases and limitations. We plan to perform a carefully conducted systematic review of individual patient data from the major randomised trials of beta-blockers in heart failure. The goals of this collaborative project are to clarify the overall efficacy of beta-blockers and identify sub-groups that show particular benefit, thereby increasing the use of beta-blockers, reducing adverse clinical outcomes and the high costs associated with this condition.

Conditions

Heart Failure

Keywords

Beta blocker; Heart Failure; Meta analysis; Individual patient data

Outcome Measures

Primary Outcomes (1)

• Beta-blocker therapy improves overall mortality and morbidity in symptomatic heart failure in an individual patient meta-analysis

  variable (time to event)

Secondary Outcomes (6)

• Beta-blocker therapy improves mortality and morbidity in both elderly patients and women

  variable (time to event)

• Beta-blocker therapy improves mortality and morbidity in patients with co-morbidities (diabetes, renal dysfunction, COPD, peripheral arterial disease or atrial fibrillation)

  variable (time to event)

• The benefit of beta-blockers is not modified by concomitant cardiovascular therapy

  variable (time to event)

• The benefit of beta-blockers is independent of left ventricular ejection fraction at baseline

  variable (time to event)

• The clinical benefit is dependent on the resting heart rate achieved whatever the dose achieved or agent used

  variable (time to event)

Study Arms (2)

Beta blocker

Drug: Beta blocker

Placebo

Other: Placebo

Interventions

Beta blocker DRUG

as determined by individual study

Also known as: Metoprolol, Bucindolol, Carvedilol, Bisoprolol, Nebivolol

Beta blocker

Placebo OTHER

in addition to usual care

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Meta-Analysis of randomised controlled trials investigating mortality \& morbidity of placebo versus beta-blockers in heart failure

You may qualify if:

• Randomised control trials of beta-blocker versus control in patients with documented heart failure
• Unconfounded trials only (in which one treatment group differed from another only by the beta-blocker therapy of interest)
• Randomization process precluded prior knowledge of the next treatment (for example trials in which treatment allocation was alternate or based on odd or even dates would not be included)

You may not qualify if:

• Trial sample size of less than 300 patients

Sponsors & Collaborators

• Royal Brompton & Harefield NHS Foundation Trust: lead
• University of Oxford: collaborator

Study Sites (2)

Clinical Trials & Evaluation Unit, Royal Brompton Hospital

London, United Kingdom

Location

Centre for Statistics in Medicine, University of Oxford

Oxford, United Kingdom

Location

Related Publications (14)

• Waagstein F, Bristow MR, Swedberg K, Camerini F, Fowler MB, Silver MA, Gilbert EM, Johnson MR, Goss FG, Hjalmarson A. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study Group. Lancet. 1993 Dec 11;342(8885):1441-6. doi: 10.1016/0140-6736(93)92930-r.

  PMID: 7902479 BACKGROUND

• A randomized trial of beta-blockade in heart failure. The Cardiac Insufficiency Bisoprolol Study (CIBIS). CIBIS Investigators and Committees. Circulation. 1994 Oct;90(4):1765-73. doi: 10.1161/01.cir.90.4.1765.

  PMID: 7923660 BACKGROUND

• Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease. Australia/New Zealand Heart Failure Research Collaborative Group. Lancet. 1997 Feb 8;349(9049):375-80.

  PMID: 9033462 BACKGROUND

• Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, Shusterman NH. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996 May 23;334(21):1349-55. doi: 10.1056/NEJM199605233342101.

  PMID: 8614419 BACKGROUND

• The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999 Jan 2;353(9146):9-13.

  PMID: 10023943 BACKGROUND

• Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, DeMets DL; Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001 May 31;344(22):1651-8. doi: 10.1056/NEJM200105313442201.

  PMID: 11386263 BACKGROUND

• Beta-Blocker Evaluation of Survival Trial Investigators; Eichhorn EJ, Domanski MJ, Krause-Steinrauf H, Bristow MR, Lavori PW. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med. 2001 May 31;344(22):1659-67. doi: 10.1056/NEJM200105313442202.

  PMID: 11386264 BACKGROUND

• Flather MD, Shibata MC, Coats AJ, Van Veldhuisen DJ, Parkhomenko A, Borbola J, Cohen-Solal A, Dumitrascu D, Ferrari R, Lechat P, Soler-Soler J, Tavazzi L, Spinarova L, Toman J, Bohm M, Anker SD, Thompson SG, Poole-Wilson PA; SENIORS Investigators. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J. 2005 Feb;26(3):215-25. doi: 10.1093/eurheartj/ehi115. Epub 2005 Jan 9.

  PMID: 15642700 BACKGROUND

• Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001 May 5;357(9266):1385-90. doi: 10.1016/s0140-6736(00)04560-8.

  PMID: 11356434 BACKGROUND

• Banerjee A, Pasea L, Chung SC, Direk K, Asselbergs FW, Grobbee DE, Kotecha D, Anker SD, Dyszynski T, Tyl B, Denaxas S, Lumbers RT, Hemingway H. A population-based study of 92 clinically recognized risk factors for heart failure: co-occurrence, prognosis and preventive potential. Eur J Heart Fail. 2022 Mar;24(3):466-480. doi: 10.1002/ejhf.2417. Epub 2022 Jan 26.

  PMID: 34969173 DERIVED

• Karwath A, Bunting KV, Gill SK, Tica O, Pendleton S, Aziz F, Barsky AD, Chernbumroong S, Duan J, Mobley AR, Cardoso VR, Slater K, Williams JA, Bruce EJ, Wang X, Flather MD, Coats AJS, Gkoutos GV, Kotecha D; card AIc group and the Beta-blockers in Heart Failure Collaborative Group. Redefining beta-blocker response in heart failure patients with sinus rhythm and atrial fibrillation: a machine learning cluster analysis. Lancet. 2021 Oct 16;398(10309):1427-1435. doi: 10.1016/S0140-6736(21)01638-X. Epub 2021 Aug 30.

  PMID: 34474011 DERIVED

• Kotecha D, Manzano L, Krum H, Rosano G, Holmes J, Altman DG, Collins PD, Packer M, Wikstrand J, Coats AJ, Cleland JG, Kirchhof P, von Lueder TG, Rigby AS, Andersson B, Lip GY, van Veldhuisen DJ, Shibata MC, Wedel H, Bohm M, Flather MD; Beta-Blockers in Heart Failure Collaborative Group. Effect of age and sex on efficacy and tolerability of beta blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis. BMJ. 2016 Apr 20;353:i1855. doi: 10.1136/bmj.i1855.

  PMID: 27098105 DERIVED

• Kotecha D, Holmes J, Krum H, Altman DG, Manzano L, Cleland JG, Lip GY, Coats AJ, Andersson B, Kirchhof P, von Lueder TG, Wedel H, Rosano G, Shibata MC, Rigby A, Flather MD; Beta-Blockers in Heart Failure Collaborative Group. Efficacy of beta blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis. Lancet. 2014 Dec 20;384(9961):2235-43. doi: 10.1016/S0140-6736(14)61373-8. Epub 2014 Sep 2.

  PMID: 25193873 DERIVED

• Kotecha D, Manzano L, Altman DG, Krum H, Erdem G, Williams N, Flather MD; Beta-Blockers in Heart Failure Collaborative Group. Individual patient data meta-analysis of beta-blockers in heart failure: rationale and design. Syst Rev. 2013 Jan 18;2:7. doi: 10.1186/2046-4053-2-7.

  PMID: 23327629 DERIVED

Related Links

• Monash Centre of Cardiovascular Research \& Education (CCRE) in Therapeutics

MeSH Terms

Conditions

Heart Failure

Interventions

Adrenergic beta-Antagonists; Metoprolol; bucindolol; Carvedilol; Bisoprolol; Nebivolol

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring; Ethanolamines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring

Study Officials

• Marcus Flather

  Royal Brompton Hospital, London

  STUDY CHAIR

• Luis Manzano

  Universidad de Alcala, Madrid

  STUDY CHAIR

• Dipak Kotecha

  Royal Brompton Hospital, London

  STUDY CHAIR

• Henry Krum

  Monash University, Melbourne

  STUDY CHAIR

Study Design

• Study Type: observational
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2009
• First Posted: January 30, 2009
• Study Start: August 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: May 9, 2012

Record last verified: 2009-01

Locations

GB (2)