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Kotecha D.,Clinical Trials and Evaluation Unit
Systematic reviews | Year: 2013

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. Clinical trial registration information: http://clinicaltrials.gov/ct2/show/NCT00832442. Source

Kotecha D.,University of Birmingham | Kotecha D.,Clinical Trials and Evaluation Unit | Kotecha D.,Monash University | Holmes J.,University of Oxford | And 20 more authors.
The Lancet | Year: 2014

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. Funding Menarini Farmaceutica Internazionale (administrative support grant). © 2014 Elsevier Ltd. All rights reserved. Source

Treasure T.,University College London | Fallowfield L.,University of Sussex | Lees B.,Clinical Trials and Evaluation Unit | Farewell V.,University of Cambridge
Thorax | Year: 2012

PulMiCC (Pulmonary Metastasectomy in Colorectal Cancer) is a randomised controlled trial funded by Cancer Research UK. Patients with a history of resected colorectal cancer who are found to have pulmonary metastases are first registered for evaluation and, if subsequently eligible for the trial, they are invited to be randomly allocated to 'active monitoring' or 'active monitoring with pulmonary metastasectomy'. The clinical outcomes are overall survival, relapse-free survival, lung function and patient-reported quality of life. Source

Perera D.,Kings College London | Stables R.,Liverpool Heart and Chest Hospital | Thomas M.,Kings College London | Booth J.,Clinical Trials and Evaluation Unit | And 4 more authors.
JAMA - Journal of the American Medical Association | Year: 2010

Context: Observational studies have previously reported that elective intra-aortic balloon pump (IABP) insertion may improve outcomes following high-risk percutaneous coronary intervention (PCI). To date, this assertion has not been tested in a randomized trial. Objective: To determine whether routine intra-aortic balloon counterpulsation before PCI reduces major adverse cardiac and cardiovascular events (MACCE) in patients with severe left ventricular dysfunction and extensive coronary disease. Design, Setting, and Patients: The Balloon Pump-Assisted Coronary Intervention Study, a prospective, open, multicenter, randomized controlled trial conducted in 17 tertiary referral cardiac centers in the United Kingdom between December 2005 and January 2009. Patients (n=301) had severe left ventricular dysfunction (ejection fraction ≤30%) and extensive coronary disease (Jeopardy Score ≥8/12); those with contraindications to or class I indications for IABP therapy were excluded. Intervention: Elective insertion of IABP before PCI. Main Outcome Measures: Primary end point was MACCE, defined as death, acute myocardial infarction, cerebrovascular event, or further revascularization at hospital discharge (capped at 28 days). Secondary end points included all-cause mortality at 6 months, major procedural complications, bleeding, and access-site complications. Results: MACCE at hospital discharge occurred in 15.2% (23/151) of the elective IABP and 16.0% (24/150) of the no planned IABP groups (P=.85; odds ratio [OR], 0.94 [95% confidence interval {CI}, 0.51-1.76]). All-cause mortality at 6 months was 4.6% and 7.4% in the respective groups (P=.32; OR, 0.61 [95% CI, 0.24-1.62]). Fewer major procedural complications occurred with elective IABP insertion compared with no planned IABP use (1.3% vs 10.7%, P<.001; OR, 0.11 [95% CI, 0.01-0.49]). Major or minor bleeding occurred in 19.2% and 11.3% (P=.06; OR, 1.86 [95% CI, 0.93-3.79]) and access-site complications in 3.3% and 0% (P=.06) of the elective and no planned IABP groups, respectively. Conclusions: Elective IABP insertion did not reduce the incidence of MACCE following PCI. These results do not support a strategy of routine IABP placement before PCI in all patients with severe left ventricular dysfunction and extensive coronary disease. Trial Registration isrctn.org Identifier: ISRCTN40553718; clinicaltrials.gov Identifier: NCT00910481 ©2010 American Medical Association. All rights reserved. Source

Stock C.J.,Imperial College London | Sato H.,Imperial College London | Fonseca C.,University College London | Banya W.A.S.,Clinical Trials and Evaluation Unit | And 11 more authors.
Thorax | Year: 2013

Background: A polymorphism (rs35705950) 3 kb upstream of MUC5B, the gene encoding Mucin 5 subtype B, has been shown to be associated with familial and sporadic idiopathic pulmonary fibrosis (IPF). We set out to verify whether this variant is also a risk factor for fibrotic lung disease in other settings and to confirm the published findings in a UK Caucasian IPF population. Methods: Caucasian UK healthy controls (n=416) and patients with IPF (n=110), sarcoidosis (n=180) and systemic sclerosis (SSc) (n=440) were genotyped to test for association. The SSc and sarcoidosis cohorts were subdivided according to the presence or absence of fibrotic lung disease. To assess correlation with disease progression, time to decline in forced vital capacity and/or lung carbon monoxide transfer factor was used in the IPF and SSc groups, while a persistent decline at 4 years since baseline was evaluated in patients with sarcoidosis. Results: A significant association of the MUC5B promoter single nucleotide polymorphism with IPF (p=2.04×10-17; OR 4.90, 95% CI 3.42 to 7.03) was confirmed in this UK population. The MUC5B variant was not a risk factor for lung fibrosis in patients with SSc or sarcoidosis and did not predict more rapidly progressive lung disease in any of the groups. Rather, a trend for a longer time to decline in forced vital capacity was observed in patients with IPF. Conclusions We confirm the MUC5B variant association: with IPF. We did not observe an association with lung fibrosis in the context of SSc or sarcoidosis, potentially highlighting fundamental differences in genetic susceptibility, although the limited subgroup numbers do not allow a definitive exclusion of an association. Source

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