Causes of Death in Anticoagulated Patients With Atrial Fibrillation

Abstract Background Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new strategies to further reduce the high mortality rates observed in this population. Objectives The authors sought to analyze and compar...

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Published inJournal of the American College of Cardiology Vol. 68; no. 23; pp. 2508 - 2521
Main Authors Gómez-Outes, Antonio, MD, PhD, Lagunar-Ruíz, Julián, MD, Terleira-Fernández, Ana-Isabel, MD, PhD, Calvo-Rojas, Gonzalo, MD, PhD, Suárez-Gea, Maria Luisa, PharmD, PhD, Vargas-Castrillón, Emilio, MD, PhD
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 13.12.2016
Elsevier Limited
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Abstract Abstract Background Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new strategies to further reduce the high mortality rates observed in this population. Objectives The authors sought to analyze and compare causes of death in patients receiving direct oral anticoagulants (DOAC) or warfarin for prevention of stroke and systemic embolism (SE) in AF. Methods The authors systematically searched for randomized trials of DOAC versus warfarin for prevention of stroke/SE in AF. The main outcome was mortality and independently adjudicated specific causes of death. The authors used the random effects model of meta-analysis to combine the studies. Results 71,683 patients from 4 trials were included (134,046 patient-years of follow-up). A total of 6,206 patients (9%) died during follow-up. Adjusted mortality rate was 4.72%/year (95% confidence interval [CI]: 4.19 to 5.28). Cardiac deaths accounted for 46% of all deaths, whereas nonhemorrhagic stroke/SE and hemorrhage-related deaths represented 5.7% and 5.6% of the total mortality, respectively. Compared with patients who were alive, those who died had more frequent history of heart failure (odds ratio [OR]: 1.75; 95% CI: 1.25 to 2.44), permanent/persistent AF (OR: 1.38; 95% CI: 1.25 to 1.52) and diabetes (OR: 1.37; 95% CI: 1.11 to 1.68); were more frequently male (OR: 1.24; 95% CI: 1.13 to 1.37) and older (mean difference 3.2 years; 95% CI: 1.6 to 4.8); and had a lower creatinine clearance (−9.9 ml/min; 95% CI: −11.3 to −8.4). There was a small, but significant, reduction in all-cause mortality with the DOAC versus warfarin (difference −0.42%/year; 95% CI: −0.66 to −0.18), mainly driven by a reduction in fatal bleedings. Conclusions In contemporary AF trials, most deaths were cardiac-related, whereas stroke and bleeding represented only a small subset of deaths. Interventions beyond anticoagulation are needed to further reduce mortality in AF.
AbstractList BACKGROUNDOral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new strategies to further reduce the high mortality rates observed in this population.OBJECTIVESThe authors sought to analyze and compare causes of death in patients receiving direct oral anticoagulants (DOAC) or warfarin for prevention of stroke and systemic embolism (SE) in AF.METHODSThe authors systematically searched for randomized trials of DOAC versus warfarin for prevention of stroke/SE in AF. The main outcome was mortality and independently adjudicated specific causes of death. The authors used the random effects model of meta-analysis to combine the studies.RESULTS71,683 patients from 4 trials were included (134,046 patient-years of follow-up). A total of 6,206 patients (9%) died during follow-up. Adjusted mortality rate was 4.72%/year (95% confidence interval [CI]: 4.19 to 5.28). Cardiac deaths accounted for 46% of all deaths, whereas nonhemorrhagic stroke/SE and hemorrhage-related deaths represented 5.7% and 5.6% of the total mortality, respectively. Compared with patients who were alive, those who died had more frequent history of heart failure (odds ratio [OR]: 1.75; 95% CI: 1.25 to 2.44), permanent/persistent AF (OR: 1.38; 95% CI: 1.25 to 1.52) and diabetes (OR: 1.37; 95% CI: 1.11 to 1.68); were more frequently male (OR: 1.24; 95% CI: 1.13 to 1.37) and older (mean difference 3.2 years; 95% CI: 1.6 to 4.8); and had a lower creatinine clearance (-9.9 ml/min; 95% CI: -11.3 to -8.4). There was a small, but significant, reduction in all-cause mortality with the DOAC versus warfarin (difference -0.42%/year; 95% CI: -0.66 to -0.18), mainly driven by a reduction in fatal bleedings.CONCLUSIONSIn contemporary AF trials, most deaths were cardiac-related, whereas stroke and bleeding represented only a small subset of deaths. Interventions beyond anticoagulation are needed to further reduce mortality in AF.
Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new strategies to further reduce the high mortality rates observed in this population. The authors sought to analyze and compare causes of death in patients receiving direct oral anticoagulants (DOAC) or warfarin for prevention of stroke and systemic embolism (SE) in AF. The authors systematically searched for randomized trials of DOAC versus warfarin for prevention of stroke/SE in AF. The main outcome was mortality and independently adjudicated specific causes of death. The authors used the random effects model of meta-analysis to combine the studies. 71,683 patients from 4 trials were included (134,046 patient-years of follow-up). A total of 6,206 patients (9%) died during follow-up. Adjusted mortality rate was 4.72%/year (95% confidence interval [CI]: 4.19 to 5.28). Cardiac deaths accounted for 46% of all deaths, whereas nonhemorrhagic stroke/SE and hemorrhage-related deaths represented 5.7% and 5.6% of the total mortality, respectively. Compared with patients who were alive, those who died had more frequent history of heart failure (odds ratio [OR]: 1.75; 95% CI: 1.25 to 2.44), permanent/persistent AF (OR: 1.38; 95% CI: 1.25 to 1.52) and diabetes (OR: 1.37; 95% CI: 1.11 to 1.68); were more frequently male (OR: 1.24; 95% CI: 1.13 to 1.37) and older (mean difference 3.2 years; 95% CI: 1.6 to 4.8); and had a lower creatinine clearance (−9.9 ml/min; 95% CI: −11.3 to −8.4). There was a small, but significant, reduction in all-cause mortality with the DOAC versus warfarin (difference −0.42%/year; 95% CI: −0.66 to −0.18), mainly driven by a reduction in fatal bleedings. In contemporary AF trials, most deaths were cardiac-related, whereas stroke and bleeding represented only a small subset of deaths. Interventions beyond anticoagulation are needed to further reduce mortality in AF. [Display omitted]
Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new strategies to further reduce the high mortality rates observed in this population. The authors sought to analyze and compare causes of death in patients receiving direct oral anticoagulants (DOAC) or warfarin for prevention of stroke and systemic embolism (SE) in AF. The authors systematically searched for randomized trials of DOAC versus warfarin for prevention of stroke/SE in AF. The main outcome was mortality and independently adjudicated specific causes of death. The authors used the random effects model of meta-analysis to combine the studies. 71,683 patients from 4 trials were included (134,046 patient-years of follow-up). A total of 6,206 patients (9%) died during follow-up. Adjusted mortality rate was 4.72%/year (95% confidence interval [CI]: 4.19 to 5.28). Cardiac deaths accounted for 46% of all deaths, whereas nonhemorrhagic stroke/SE and hemorrhage-related deaths represented 5.7% and 5.6% of the total mortality, respectively. Compared with patients who were alive, those who died had more frequent history of heart failure (odds ratio [OR]: 1.75; 95% CI: 1.25 to 2.44), permanent/persistent AF (OR: 1.38; 95% CI: 1.25 to 1.52) and diabetes (OR: 1.37; 95% CI: 1.11 to 1.68); were more frequently male (OR: 1.24; 95% CI: 1.13 to 1.37) and older (mean difference 3.2 years; 95% CI: 1.6 to 4.8); and had a lower creatinine clearance (-9.9 ml/min; 95% CI: -11.3 to -8.4). There was a small, but significant, reduction in all-cause mortality with the DOAC versus warfarin (difference -0.42%/year; 95% CI: -0.66 to -0.18), mainly driven by a reduction in fatal bleedings. In contemporary AF trials, most deaths were cardiac-related, whereas stroke and bleeding represented only a small subset of deaths. Interventions beyond anticoagulation are needed to further reduce mortality in AF.
Abstract Background Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new strategies to further reduce the high mortality rates observed in this population. Objectives The authors sought to analyze and compare causes of death in patients receiving direct oral anticoagulants (DOAC) or warfarin for prevention of stroke and systemic embolism (SE) in AF. Methods The authors systematically searched for randomized trials of DOAC versus warfarin for prevention of stroke/SE in AF. The main outcome was mortality and independently adjudicated specific causes of death. The authors used the random effects model of meta-analysis to combine the studies. Results 71,683 patients from 4 trials were included (134,046 patient-years of follow-up). A total of 6,206 patients (9%) died during follow-up. Adjusted mortality rate was 4.72%/year (95% confidence interval [CI]: 4.19 to 5.28). Cardiac deaths accounted for 46% of all deaths, whereas nonhemorrhagic stroke/SE and hemorrhage-related deaths represented 5.7% and 5.6% of the total mortality, respectively. Compared with patients who were alive, those who died had more frequent history of heart failure (odds ratio [OR]: 1.75; 95% CI: 1.25 to 2.44), permanent/persistent AF (OR: 1.38; 95% CI: 1.25 to 1.52) and diabetes (OR: 1.37; 95% CI: 1.11 to 1.68); were more frequently male (OR: 1.24; 95% CI: 1.13 to 1.37) and older (mean difference 3.2 years; 95% CI: 1.6 to 4.8); and had a lower creatinine clearance (−9.9 ml/min; 95% CI: −11.3 to −8.4). There was a small, but significant, reduction in all-cause mortality with the DOAC versus warfarin (difference −0.42%/year; 95% CI: −0.66 to −0.18), mainly driven by a reduction in fatal bleedings. Conclusions In contemporary AF trials, most deaths were cardiac-related, whereas stroke and bleeding represented only a small subset of deaths. Interventions beyond anticoagulation are needed to further reduce mortality in AF.
Background Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new strategies to further reduce the high mortality rates observed in this population. Objectives The authors sought to analyze and compare causes of death in patients receiving direct oral anticoagulants (DOAC) or warfarin for prevention of stroke and systemic embolism (SE) in AF. Methods The authors systematically searched for randomized trials of DOAC versus warfarin for prevention of stroke/SE in AF. The main outcome was mortality and independently adjudicated specific causes of death. The authors used the random effects model of meta-analysis to combine the studies. Results 71,683 patients from 4 trials were included (134,046 patient-years of follow-up). A total of 6,206 patients (9%) died during follow-up. Adjusted mortality rate was 4.72%/year (95% confidence interval [CI]: 4.19 to 5.28). Cardiac deaths accounted for 46% of all deaths, whereas nonhemorrhagic stroke/SE and hemorrhage-related deaths represented 5.7% and 5.6% of the total mortality, respectively. Compared with patients who were alive, those who died had more frequent history of heart failure (odds ratio [OR]: 1.75; 95% CI: 1.25 to 2.44), permanent/persistent AF (OR: 1.38; 95% CI: 1.25 to 1.52) and diabetes (OR: 1.37; 95% CI: 1.11 to 1.68); were more frequently male (OR: 1.24; 95% CI: 1.13 to 1.37) and older (mean difference 3.2 years; 95% CI: 1.6 to 4.8); and had a lower creatinine clearance (-9.9 ml/min; 95% CI: -11.3 to -8.4). There was a small, but significant, reduction in all-cause mortality with the DOAC versus warfarin (difference -0.42%/year; 95% CI: -0.66 to -0.18), mainly driven by a reduction in fatal bleedings. Conclusions In contemporary AF trials, most deaths were cardiac-related, whereas stroke and bleeding represented only a small subset of deaths. Interventions beyond anticoagulation are needed to further reduce mortality in AF.
Author Calvo-Rojas, Gonzalo, MD, PhD
Terleira-Fernández, Ana-Isabel, MD, PhD
Vargas-Castrillón, Emilio, MD, PhD
Lagunar-Ruíz, Julián, MD
Gómez-Outes, Antonio, MD, PhD
Suárez-Gea, Maria Luisa, PharmD, PhD
Author_xml – sequence: 1
  fullname: Gómez-Outes, Antonio, MD, PhD
– sequence: 2
  fullname: Lagunar-Ruíz, Julián, MD
– sequence: 3
  fullname: Terleira-Fernández, Ana-Isabel, MD, PhD
– sequence: 4
  fullname: Calvo-Rojas, Gonzalo, MD, PhD
– sequence: 5
  fullname: Suárez-Gea, Maria Luisa, PharmD, PhD
– sequence: 6
  fullname: Vargas-Castrillón, Emilio, MD, PhD
BackLink https://www.ncbi.nlm.nih.gov/pubmed/27931607$$D View this record in MEDLINE/PubMed
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2016 American College of Cardiology Foundation
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Issue 23
Keywords RR
high-dose
rivaroxaban
odds ratio
systemic embolism
DOAC
direct oral anticoagulant
atrial fibrillation
SE
TTR
dabigatran
OR
time within therapeutic range
AF
CI
cardiovascular
apixaban
stroke
VKA
relative risk
vitamin K antagonist
warfarin
CV
LD
confidence interval
low-dose
HD
Language English
License http://www.elsevier.com/open-access/userlicense/1.0
Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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Snippet Abstract Background Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to...
Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new strategies to...
Background Oral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new...
BACKGROUNDOral anticoagulation reduces the risk of mortality in atrial fibrillation (AF), but examination of the causes of death is essential to design new...
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SubjectTerms Administration, Oral
Aged
Anticoagulants
Anticoagulants - therapeutic use
apixaban
atrial fibrillation
Atrial Fibrillation - complications
Atrial Fibrillation - drug therapy
Atrial Fibrillation - mortality
Cardiac arrhythmia
Cardiology
Cardiovascular
Cause of Death - trends
Clinical trials
dabigatran
Embolisms
Female
Follow-Up Studies
Humans
Internal Medicine
Male
Meta-analysis
Mortality
Patients
Quality
Registries
Retrospective Studies
rivaroxaban
Software
Stroke
Stroke - etiology
Stroke - mortality
Stroke - prevention & control
Studies
Survival Rate - trends
United States - epidemiology
warfarin
Title Causes of Death in Anticoagulated Patients With Atrial Fibrillation
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https://dx.doi.org/10.1016/j.jacc.2016.09.944
https://www.ncbi.nlm.nih.gov/pubmed/27931607
https://www.proquest.com/docview/1848797612
https://search.proquest.com/docview/1847890629
https://search.proquest.com/docview/1855079145
Volume 68
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