Individual patient data meta-analysis of beta-blockers in heart failure: rationale and design

Dipak Kotecha,Luis Manzano,Nicola Williams,Douglas G Altman,Marcus D Flather,Guliz Erdem,Henry Krum

doi:10.1186/2046-4053-2-7

Abstract

The Beta-Blockers in Heart Failure Collaborative Group (BB-HF) was formed to obtain and analyze individual patient data from the major randomized controlled trials of beta-blockers in heart failure. Even though beta-blockers are an established treatment for heart failure, uptake is still sub-optimal. Further, the balance of efficacy and safety remains uncertain for common groups including older persons, women, those with impaired renal function and diabetes. Our aim is to provide clinicians with a thorough and definitive evidence-based assessment of these agents. We have identified 11 large randomized trials of beta-blockers versus placebo in heart failure and plan to meta-analyze the data on an individual patient level. In total, these trials have enrolled 18,630 patients. Uniquely, the BB-HF group has secured access to the individual data for all of these trials, with the participation of key investigators and pharmaceutical companies.Our principal objectives include deriving an overall estimate of efficacy for all-cause mortality and cardiovascular hospitalization. Importantly, we propose a statistically-robust sub-group assessment according to age, gender, diabetes and other key factors; analyses which are only achievable using an individual patient data meta-analysis. Further, we aim to provide an assessment of economic benefit and develop a risk model for the prognosis of patients with chronic heart failure.This paper outlines inclusion criteria, search strategies, outcome measures and planned statistical analyses.Trial registrationClinical trial registration information: http://clinicaltrials.gov/ct2/show/NCT00832442

Highlights

Heart failure (HF) is a major public health problem with both incidence and prevalence rising rapidly along with associated healthcare costs, estimated to be $39.2 billion in the United States and £625 million per year in the UK [1,2]
Despite a wealth of information identifying the overall benefits of beta-blockers in HF for morbidity and mortality, prescription rates remain sub-optimal with consequence for both patients and healthcare providers
Current data are limited to those enrolled in the randomized controlled trials (RCTs) and lack sufficient statistical power to examine the harm and benefits of treatment in important patient subgroups

Summary

Introduction

Heart failure (HF) is a major public health problem with both incidence and prevalence rising rapidly along with associated healthcare costs, estimated to be $39.2 billion in the United States and £625 million per year in the UK [1,2]. The percentage of eligible patients prescribed beta-blockers increased between the first and second Euro Heart Failure surveys, a substantial number of patients remain untreated or receive sub-maximal therapy [5,6]. Those at the greatest risk of death are less likely to receive evidence-based therapy after a HF hospitalization [7]. The reasons for this are multi-factorial and include a long entrenched belief that starting betablockers in HF may make symptoms worse or that betablockers should only be commenced in specialized clinics. There has been concern that the evidence-base is not representative of broader clinical practice and that common patient groups, including older persons, those with impaired renal function and diabetes may not benefit

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