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Biomarkers Associated With Clinical Events in Atrial Fibrillation
Quick Takes
- Serum biomarkers may help stratify the risks and benefits of antithrombotic therapy in patients with atrial fibrillation.
- Elevated hsTnT and NT-proBNP concentrations, as well as increasing values over time, were each associated with an increased risk of stroke and systemic embolism.
- Higher GDF-15 concentration and increasing values over time were associated with major bleeding.
Study Questions:
Do changes in serum biomarkers predict stroke or systemic embolism or bleeding in patients with atrial fibrillation (AF)?
Methods:
This analysis comes from a substudy of the ENGAGE AF-TIMI 48 trial that compared edoxaban to warfarin for stroke prevention in patients with AF. The biomarkers evaluated were high-sensitivity cardiac troponin T (hsTnT), N-terminal pro–B-type natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15). The biomarkers were evaluated at randomization and at 1 year. The primary outcomes were stroke, systemic embolism, and major bleeding.
Results:
More than 6,000 patients were included in the study. The absolute change in biomarker concentration over 12 months was very small, although about 10% of patients went from low to high individual biomarker concentrations. There was no association between type of anticoagulation and change in biomarker concentration.
In adjusted analyses, high levels of hsTnT and NT-proBNP were associated with a more than doubling of the risk of stroke and systemic embolism while elevated GDF-15 concentration was associated with an increased risk of bleeding. An increase in concentration of hsTnT and NT-proBNP over the course of the study, compared with patients with stable values, was associated with an increased risk of stroke and systemic embolism. GDF-15 increases were associated with an increased risk of major bleeding.
Conclusions:
Absolute levels, as well as changes in serum biomarkers over time, are associated with clinical events in patients with AF.
Perspective:
Patients with AF are at risk of stroke and systemic embolism as well as bleeding. While clinical prediction scores, such as CHA2DS2-VASc, and HAS-BLED, risk stratify patients, additional precision could help clinical decision making regarding antithrombotic therapy. Biomarkers, such as the ones evaluated in this study, may help tailor treatment for patients with AF as well as more accurately define the risks and benefits of treatment over time. This study was done in anticoagulated patients and it is unclear if the findings apply to patients with AF who are not anticoagulated. While biomarker-based risk assessment may have epidemiologic significance, given the marked benefit of anticoagulation in reducing the risk of stroke and systemic embolism in patients with AF and the improved safety profile of direct oral anticoagulants, compared to warfarin, it is unclear if the information from biomarkers has enough predictive value to impact clinical management.
Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Prevention, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias
Keywords: Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Biomarkers, Embolism, Fibrinolytic Agents, Growth Differentiation Factor 15, Hemorrhage, Natriuretic Peptide, Brain, Peptide Fragments, Risk Assessment, Secondary Prevention, Stroke, Troponin T, Vascular Diseases, Warfarin
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