Dipak Kotecha1, Jane Holmes2, Henry Krum3, Douglas G Altman2, Luis Manzano4, John G F Cleland5, Gregory Y H Lip6, Andrew J S Coats7, Bert Andersson8, Paulus Kirchhof9, Thomas G von Lueder10, Hans Wedel11, Giuseppe Rosano12, Marcelo C Shibata13, Alan Rigby14, Marcus D Flather15. 1. University of Birmingham Centre for Cardiovascular Sciences, Birmingham, UK; Clinical Trials and Evaluation Unit, Royal Brompton and Harefield NHS Trust, London, UK; Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, VIC, Australia. Electronic address: d.kotecha@bham.ac.uk. 2. Centre for Statistics in Medicine, University of Oxford, Oxford, UK. 3. Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, VIC, Australia. 4. Internal Medicine Department, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, Spain. 5. National Heart and Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, UK; Hull York Medical School, University of Hull, Kingston upon Hull, UK. 6. University of Birmingham Centre for Cardiovascular Sciences, Birmingham, UK; City Hospital, Sandwell and West Birmingham NHS Trust, Birmingham, UK. 7. Monash University, Melbourne, VIC, Australia; Warwick University, Warwick, UK. 8. Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. 9. University of Birmingham Centre for Cardiovascular Sciences, Birmingham, UK; City Hospital, Sandwell and West Birmingham NHS Trust, Birmingham, UK; Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany. 10. Centre of Cardiovascular Research and Education in Therapeutics, Monash University, Melbourne, VIC, Australia; Department of Cardiology, Oslo University Hospital, Oslo, Norway. 11. Nordic School of Public Health, Gothenburg, Sweden. 12. Department of Medical Sciences, Instituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, Rome, Italy. 13. Division of Cardiology, University of Alberta, Edmonton, Canada. 14. Academic Cardiology, Castle Hill Hospital, Kingston upon Hull, UK. 15. Norwich Medical School, University of East Anglia, Norwich, UK.
Abstract
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).
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).
Authors: Bart A Mulder; Kevin Damman; Dirk J Van Veldhuisen; Isabelle C Van Gelder; Michiel Rienstra Journal: Clin Cardiol Date: 2017-05-17 Impact factor: 2.882
Authors: Hanna Fröhlich; Lorella Torres; Tobias Täger; Dieter Schellberg; Anna Corletto; Syed Kazmi; Kevin Goode; Morten Grundtvig; Torstein Hole; Hugo A Katus; John G F Cleland; Dan Atar; Andrew L Clark; Stefan Agewall; Lutz Frankenstein Journal: Clin Res Cardiol Date: 2017-04-22 Impact factor: 5.460