The Use of Biomarkers to Predict Specific Causes of Death in Patients with Atrial Fibrillation: Insights from the ARISTOTLE Trial

Background —Atrial fibrillation (AF) is associated with an increased risk of death. High-sensitivity troponin-T, growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and interleukin-6 levels are predictive of cardiovascular (CV) events and total and CV death in anticoagulated AF patients. The prognostic utility of these biomarkers for cause-specific death is unknown. Methods —The ARISTOTLE trial randomized 18,201 patients with AF to apixaban or warfarin. Biomarkers were measured at randomization in 14,798 patients (1.9 years median follow-up). Cox-models were used to identify clinical variables and biomarkers independently associated with each specific cause of death. Results —In total 1,272 patients died: 652 (51%) CV; 32 (3%) bleeding; and 588 (46%) non-CV/non-bleeding deaths. Among CV-deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure (HF), and 106 stroke/systemic embolism (SE) (16%) deaths. Biomarkers were the strongest predictors of cause-specific death: a doubling of troponin-T was most strongly associated with sudden death (HR 1.48; p 0.001) followed by troponin-T (HR 1.45; p Conclusions —Biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients9 risks for different causes of death. These data suggest a potential role of biomarkers for identification of patients at risk for different causes of death in patients anticoagulated for AF. Clinical Trial Registration —URL: https://www.clinicaltrials.gov Unique Identifier: NCT00412984.