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Cited by 314Atrial Fibrillation Management and OutcomesVenous Thromboembolism Diagnosis and ManagementAcute Ischemic Stroke Management

Causes of Death and Influencing Factors in Patients With Atrial Fibrillation: A Competing-Risk Analysis From the Randomized Evaluation of Long-Term Anticoagulant Therapy Study

Marijon, Eloi, Le Heuzey, Jean-Yves, Connolly, Stuart, Yang, Sean, Pogue, Janice, Brueckmann, Martina, Eikelboom, John, Themeles, Ellison +3 more·2013·Circulation
DOI 10.1161/circulationaha.112.000491
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Abstract

BACKGROUND: Atrial fibrillation is associated with increased mortality, but the specific causes of death and their predictors have not been described among patients on effective anticoagulant therapy. METHODS AND RESULTS: The Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial randomized 18 113 patients (age, 71.5 ± 9 years; male, 64%; CHADS2 score, 2.1 ± 1) to receive dabigatran or warfarin. Median follow-up was 2 years, and complete follow-up was achieved in 99.9% of patients. All deaths were categorized by the investigators using prespecified definitions followed by central adjudication. Overall, 1371 deaths occurred (annual mortality rate, 3.84%; 95% confidence interval [CI], 3.64-4.05). Cardiac deaths (sudden cardiac death and progressive heart failure) accounted for 37.4% of all deaths, whereas stroke- and hemorrhage-related deaths represented 9.8% of the total mortality. An examination of the causes of death according to dabigatran or warfarin showed that dabigatran significantly reduced vascular (embolism and hemorrhage-related) mortality (relative risk, 0.63; 95% CI, 0.45-0.88; P=0.007), whereas other causes of death were similar between treatments, including cardiac mortality (relative risk, 0.96; 95% CI, 0.80-1.15; P=0.638). The two strongest independent predictors of cardiac death in this population were heart failure (hazard ratio, 3.02; 95% CI, 2.45-3.73; P<0.0001), and prior myocardial infarction (hazard ratio, 2.05; 95% CI, 1.61-2.62; P<0.0001). CONCLUSIONS: The majority of deaths are not related to stroke in a contemporary anticoagulated atrial fibrillation population. These results emphasize the need to identify interventions beyond effective anticoagulation to further reduce mortality in atrial fibrillation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

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  • A minority of deaths in AF are related to stroke, while sudden cardiac death and death from progressive heart failure are more frequent.

    “A minority of these deaths are related to stroke, while sudden cardiac death and death from progressive heart failure are more frequent, emphasizing the need for interventions beyond anticoagulation.43,44”

    From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [43]

  • The association of QTc interval to risk of AF development is J-shaped, with both a shorter and longer QTc interval associated with increased risk of AF.

    “the Copenhagen ECG Study, which included ECGs from almost 290,000 individuals, showed that the association of QTc interval to risk of AF development is J-shaped, with both a shorter and longer QTc interval associated with increased risk of AF.159”

    From Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis (2016) · cites this paper as [159]

  • Both long and short PR intervals are associated with increased risk of AF in women, whereas only longer PR intervals are associated with AF in men.

    “the Copenhagen ECG Study showed that both long and short PR intervals were associated with increased risk of AF in women, whereas only longer PR intervals were associated with AF in men.159”

    From Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis (2016) · cites this paper as [159]

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Authors
Marijon, E., Le Heuzey, J.-Y., Connolly, S., Yang, S., Pogue, J., Brueckmann, M., Eikelboom, J., Themeles, E., Ezekowitz, M., Wallentin, L., & Yusuf, S.
Affiliations
  • From the Paris Cardiovascular Research Center, Paris, France (E.M.); Paris Descartes University, Paris, France (E.M., J.-Y.L.H.); European Georges Pompidou Hospital, Paris, France (E.M., J.-Y.L.H.); Population Health Research Institute, McMaster University, Hamilton Health Sciences, Hamilton, ON, Canada (S.C., S.Y., J.P., J.E., E.T., S.Y.); Boehringer Ingelheim Pharma GmbH &amp; Co KG, Clinical Development and Medical Affairs, Ingelheim am Rhein, Germany, and Medical Faculty Mannheim of the...
  • Uppsala University Hospital (SE)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2013-11-12
Volume
128
Issue
20
Pages
2192-2201
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.112.000491
OpenAlex
W2121149747
Cited by
314
References
40
Citations by year
2026: 4 · 2025: 16 · 2024: 19 · 2023: 25 · 2022: 24 · 2021: 34 · 2020: 25 · 2019: 27 · 2018: 30 · 2017: 40 · 2016: 29 · 2015: 19 · 2014: 22
FWCI
15.87
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
  • Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
  • Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
Keywords
atrial fibrillation, causes of death, mortality, dabigatran, warfarin, anticoagulation, cardiovascular mortality, heart failure, sudden cardiac death, hemorrhagic stroke, embolic stroke, mortality risk factors, old myocardial infarction
MeSH terms
Dabigatran, Aged, Aged, 80 and over, Anticoagulants, Antithrombins, Atrial Fibrillation, Benzimidazoles, Cause of Death, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Male, Middle Aged, Predictive Value of Tests, Risk Factors, Warfarin, beta-Alanine, Incidence

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