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?

Methods:

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.

Results:

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.

Conclusions:

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.

Perspective:

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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