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

• Published in: Circulation (New York, N.Y.) Vol. 128; no. 20; pp. 2192 - 2201
• Main Authors: Marijon, Eloi, Le Heuzey, Jean-Yves, Connolly, Stuart, Yang, Sean, Pogue, Janice, Brueckmann, Martina, Eikelboom, John, Themeles, Ellison, Ezekowitz, Michael, Wallentin, Lars, Yusuf, Salim
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD by the American College of Cardiology Foundation and the American Heart Association, Inc 12.11.2013; Lippincott Williams & Wilkins
• Subjects: Aged; Aged, 80 and over; Anticoagulants - administration & dosage; Antithrombins - administration & dosage; Atrial Fibrillation - drug therapy; Atrial Fibrillation - mortality; Benzimidazoles - administration & dosage; beta-Alanine - administration & dosage; beta-Alanine - analogs & derivatives; Biological and medical sciences; Blood and lymphatic vessels; Blood. Blood coagulation. Reticuloendothelial system; cardiac; Cardiac dysrhythmias; Cardiology. Vascular system; Cause of Death; Dabigatran; death; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Dose-Response Relationship, Drug; embolism; Female; Follow-Up Studies; Heart; heart failure; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; hemorrhage; Humans; Incidence; Male; Medical sciences; Middle Aged; mortality; Pharmacology. Drug treatments; Predictive Value of Tests; Risk Factors; stroke; sudden; Warfarin - administration & dosage; Heart; Prognosis; Arrhythmia; Cardiovascular disease; Anticoagulant; Competing risks; Epidemiology; Hemorrhage; Vascular disease; Randomization; Heart disease; Cause; Cardiology; Cerebrovascular disease; Human; Heart failure; Evaluation; Nervous system diseases; Stroke; Acute; Atrial fibrillation; Mortality; Competing risk; Patient; Sudden; Risk analysis; Long term; Excitability disorder; Embolism; Cerebral disorder; death, sudden, cardiac; Central nervous system disease; Death; Circulatory system; Causality; mortality; heart failure; embolism; stroke; hemorrhage
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.112.000491

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—URLhttp://www.clinicaltrials.gov. Unique identifierNCT00262600.