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Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data

Objective To clarify the impact of digoxin on death and clinical outcomes across all observational and randomised controlled trials, accounting for study designs and methods. Data sources and study selection Comprehensive literature search of Medline, Embase, the Cochrane Library, reference lists, a...

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Autores principales: Ziff, Oliver J, Lane, Deirdre A, Samra, Monica, Griffith, Michael, Kirchhof, Paulus, Lip, Gregory Y H, Steeds, Richard P, Townend, Jonathan, Kotecha, Dipak
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group Ltd. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553205/
https://www.ncbi.nlm.nih.gov/pubmed/26321114
http://dx.doi.org/10.1136/bmj.h4451
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author Ziff, Oliver J
Lane, Deirdre A
Samra, Monica
Griffith, Michael
Kirchhof, Paulus
Lip, Gregory Y H
Steeds, Richard P
Townend, Jonathan
Kotecha, Dipak
author_facet Ziff, Oliver J
Lane, Deirdre A
Samra, Monica
Griffith, Michael
Kirchhof, Paulus
Lip, Gregory Y H
Steeds, Richard P
Townend, Jonathan
Kotecha, Dipak
author_sort Ziff, Oliver J
collection PubMed
description Objective To clarify the impact of digoxin on death and clinical outcomes across all observational and randomised controlled trials, accounting for study designs and methods. Data sources and study selection Comprehensive literature search of Medline, Embase, the Cochrane Library, reference lists, and ongoing studies according to a prospectively registered design (PROSPERO: CRD42014010783), including all studies published from 1960 to July 2014 that examined treatment with digoxin compared with control (placebo or no treatment). Data extraction and synthesis Unadjusted and adjusted data pooled according to study design, analysis method, and risk of bias. Main outcome measures Primary outcome (all cause mortality) and secondary outcomes (including admission to hospital) were meta-analysed with random effects modelling. Results 52 studies were systematically reviewed, comprising 621 845 patients. Digoxin users were 2.4 years older than control (weighted difference 95% confidence interval 1.3 to 3.6), with lower ejection fraction (33% v 42%), more diabetes, and greater use of diuretics and anti-arrhythmic drugs. Meta-analysis included 75 study analyses, with a combined total of 4 006 210 patient years of follow-up. Compared with control, the pooled risk ratio for death with digoxin was 1.76 in unadjusted analyses (1.57 to 1.97), 1.61 in adjusted analyses (1.31 to 1.97), 1.18 in propensity matched studies (1.09 to 1.26), and 0.99 in randomised controlled trials (0.93 to 1.05). Meta-regression confirmed that baseline differences between treatment groups had a significant impact on mortality associated with digoxin, including markers of heart failure severity such as use of diuretics (P=0.004). Studies with better methods and lower risk of bias were more likely to report a neutral association of digoxin with mortality (P<0.001). Across all study types, digoxin led to a small but significant reduction in all cause hospital admission (risk ratio 0.92, 0.89 to 0.95; P<0.001; n=29 525). Conclusions Digoxin is associated with a neutral effect on mortality in randomised trials and a lower rate of admissions to hospital across all study types. Regardless of statistical analysis, prescription biases limit the value of observational data.
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spelling pubmed-45532052015-09-04 Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data Ziff, Oliver J Lane, Deirdre A Samra, Monica Griffith, Michael Kirchhof, Paulus Lip, Gregory Y H Steeds, Richard P Townend, Jonathan Kotecha, Dipak BMJ Research Objective To clarify the impact of digoxin on death and clinical outcomes across all observational and randomised controlled trials, accounting for study designs and methods. Data sources and study selection Comprehensive literature search of Medline, Embase, the Cochrane Library, reference lists, and ongoing studies according to a prospectively registered design (PROSPERO: CRD42014010783), including all studies published from 1960 to July 2014 that examined treatment with digoxin compared with control (placebo or no treatment). Data extraction and synthesis Unadjusted and adjusted data pooled according to study design, analysis method, and risk of bias. Main outcome measures Primary outcome (all cause mortality) and secondary outcomes (including admission to hospital) were meta-analysed with random effects modelling. Results 52 studies were systematically reviewed, comprising 621 845 patients. Digoxin users were 2.4 years older than control (weighted difference 95% confidence interval 1.3 to 3.6), with lower ejection fraction (33% v 42%), more diabetes, and greater use of diuretics and anti-arrhythmic drugs. Meta-analysis included 75 study analyses, with a combined total of 4 006 210 patient years of follow-up. Compared with control, the pooled risk ratio for death with digoxin was 1.76 in unadjusted analyses (1.57 to 1.97), 1.61 in adjusted analyses (1.31 to 1.97), 1.18 in propensity matched studies (1.09 to 1.26), and 0.99 in randomised controlled trials (0.93 to 1.05). Meta-regression confirmed that baseline differences between treatment groups had a significant impact on mortality associated with digoxin, including markers of heart failure severity such as use of diuretics (P=0.004). Studies with better methods and lower risk of bias were more likely to report a neutral association of digoxin with mortality (P<0.001). Across all study types, digoxin led to a small but significant reduction in all cause hospital admission (risk ratio 0.92, 0.89 to 0.95; P<0.001; n=29 525). Conclusions Digoxin is associated with a neutral effect on mortality in randomised trials and a lower rate of admissions to hospital across all study types. Regardless of statistical analysis, prescription biases limit the value of observational data. BMJ Publishing Group Ltd. 2015-08-30 /pmc/articles/PMC4553205/ /pubmed/26321114 http://dx.doi.org/10.1136/bmj.h4451 Text en © Ziff et al 2015 http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Ziff, Oliver J
Lane, Deirdre A
Samra, Monica
Griffith, Michael
Kirchhof, Paulus
Lip, Gregory Y H
Steeds, Richard P
Townend, Jonathan
Kotecha, Dipak
Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data
title Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data
title_full Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data
title_fullStr Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data
title_full_unstemmed Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data
title_short Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data
title_sort safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553205/
https://www.ncbi.nlm.nih.gov/pubmed/26321114
http://dx.doi.org/10.1136/bmj.h4451
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