Biomarkers to Predict Causes of Death in Atrial Fibrillation

Study Questions:

What is the prognostic utility of high-sensitivity troponin T, growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and interleukin-6 levels in predicting cardiovascular (CV) events and total and CV death in anticoagulated atrial fibrillation (AF) patients?


The study cohort was comprised of 18,201 AF patients randomized to apixaban or warfarin in the ARISTOTLE trial. Biomarkers were measured at randomization in 14,798 patients (median 1.9-year follow-up). The study authors utilized Cox models to identify clinical variables and biomarkers independently associated with each specific cause of death.


In this study, 1,272 patients (7%) died: 652 (51%) CV, 32 (3%) bleeding, and 588 (46%) non-CV/nonbleeding deaths. Among CV deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure (HF), and 106 (16%) stroke/systemic embolism (SE) deaths. Of patients with available biomarker data (n = 14,798), there were 1,075 (7.3%) deaths; the overall distribution of causes of death and the baseline demographics were similar compared with the ARISTOTLE population. Among non-CV deaths, malignancy was the most common identified cause of death (n = 126, 21% of all non-CV deaths). The study authors found that biomarkers are the strongest predictors of cause-specific death: a doubling of troponin T was most strongly associated with sudden death (hazard ratio [HR], 1.48; p < 0.001), NT-proBNP with HF death (HR, 1.62; p < 0.001), and GDF-15 with bleeding death (HR, 1.72; p = 0.028). Prior stroke/SE (HR, 2.58; p > 0.001) followed by troponin T (HR, 1.45; p < 0.0029) were the most predictive for stroke/SE death. Adding all biomarkers to clinical variables improved discrimination for each cause-specific death.


The study authors concluded that biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients’ risks for different causes of death.


This is an important study because it suggests that in anticoagulated AF patients, nonstroke causes of death are significant, and that biomarkers are predictive of cause-specific death. These findings should prompt the search for therapies to reduce nonstroke causes of death in anticoagulated AF patients.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Prevention, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Biological Markers, Death, Sudden, Cardiac, Embolism, Heart Failure, Hemorrhage, Interleukin-6, Natriuretic Peptide, Brain, Secondary Prevention, Stroke, Troponin, Troponin T, Warfarin

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