Grant: Travel Awards - Institute Community Support

Introduction: While oral anticoagulation reduces the risk of stroke and stroke-related death in patients with atrial fibrillation (AF), the specific causes of death are poorly understood. We assessed association between various biomarkers (blood proteins) and causes of death in patients from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Methods: 18,201 patients with AF and at least one stroke risk factor were enrolled in the ARISTOTLE trial. The following biomarkers were available on 14798 patients: troponin T (cTnT-hs), NT-proBNP, GDF-15, and interleukin-6. Results: In total 1272 patients died. For the majority of causes of deaths, the biomarkers showed stronger associations than known clinical variables. cTnT-hs and NT-proBNP showed the strongest associations with sudden death. NT-proBNP had the strongest association with heart failure death. The strongest indicators of stroke-related mortality were history of stroke, cTnT-hs, age, and NT-proBNP. Although based on few events, the strongest associations with fatal bleeding were found for GDF-15 and age. Our results have three main findings: (1) In anticoagulated patients with AF, the majority of deaths were cardiovascular, most commonly sudden death and heart failure; (2) Biomarkers indicating cardiovascular dysfunction had stronger association with sudden and heart failure death than any clinical variable; and (3) Biomarkers were better able to predict cause of specific causes of death. Conclusion: Strategies to improve outcomes in anticoagulated AF patients should include treatments for co-morbidities such as congestive heart failure. These results support the role of using biomarkers in combination with key clinical variables to accurately assess the risk of cause-specific mortality in a population of patients with AF and stroke risk factors.