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
Background—Atrial fibrillation (AF) is associated with increased mortality, but the specific causes of death and their predictors have not been described among patients under effective anticoagulant therapy.
Methods and Results—The Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial randomized 18,113 patients (71.5±9 years, 64% males, 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 of 3.84%, 95%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. On examining causes of death according to dabigatran or warfarin, dabigatran significantly reduced vascular (embolism and hemorrhage-related) mortality (RR: 0.63, 95%CI 0.45-0.88, P=0.007), while other causes of death were similar between treatments, including cardiac mortality (RR: 0.96, 95%CI 0.80-1.15, P=0.638). The strongest independent predictors of cardiac death in this population were heart failure (HR: 3.02, 95%CI 2.45-3.73, P<0.0001), intraventricular conduction delay (HR: 1.99, 95%CI 1.61-2.47, P<0.0001), and prior myocardial infarction (HR: 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 AF population. These results emphasize the need to identify interventions beyond effective anticoagulation, in order to further reduce mortality in AF.
Clinical Trial Registration Information—http://www.clinicaltrials.gov. Identifier: NCT00262600.
- Received December 7, 2012.
- Revision received August 5, 2013.
- Accepted August 23, 2013.