Serial assessment of biomarkers and the risk of stroke or systemic embolism and bleeding in patients with atrial fibrillation in the ENGAGE AF-TIMI 48 trial. (24th March 2021)

• Record Type: Journal Article
• Authors: Oyama, Kazuma; Giugliano, Robert P; Berg, David D; Ruff, Christian T; Jarolim, Petr; Tang, Minao; Murphy, Sabina A; Lanz, Hans J; Grosso, Michael A; Antman, Elliott M; Braunwald, Eugene; Morrow, David A
• Is Part Of: European heart journal. Volume 42:Number 17(2021)
• Page Start: 1698
• Page End: 1706
• Publication Date: 2021-03-24
• Subjects: Atrial fibrillation -- Biomarkers -- Stroke -- Haemorrhage -- Risk assessment; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehab141
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Aims: We investigated whether patients with atrial fibrillation (AF) demonstrate detectable changes in biomarkers including high-sensitivity troponin T (hsTnT), N-terminal B-type natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) over 12 months and whether such changes from baseline to 12 months are associated with the subsequent risk of stroke or systemic embolic events (S/SEE) and bleeding. Methods and results: ENGAGE AF-TIMI 48 was a randomized trial of the oral factor Xa inhibitor edoxaban in patients with AF and a CHADS2 score of ≥2. We performed a nested prospective biomarker study in 6308 patients, analysing hsTnT, NT-proBNP, and GDF-15 at baseline and 12 months. hsTnT was dynamic in 46.9% (≥2 ng/L change), NT-proBNP in 51.9% (≥200 pg/mL change), GDF-15 in 45.6% (≥300 pg/mL change) during 12 months. In a Cox regression model, upward changes in log2 -transformed hsTnT and NT-proBNP were associated with increased risk of S/SEE [adjusted hazard ratio (adj-HR) 1.74; 95% confidence interval (CI) 1.36–2.23 and adj-HR 1.27; 95% CI 1.07–1.50, respectively] and log2 -transformed GDF-15 with bleeding (adj-HR 1.40; 95% CI 1.02–1.92). Reassessment of ABC-stroke (age, prior stroke/transient ischaemic attack, hsTnT, and NT-proBNP) and ABC-bleeding (age, prior bleeding, haemoglobin, hsTnT, and GDF-15) risk scores at 12 months accurately reclassified a significant proportion of patients compared with their baseline risk [net reclassification improvement (NRI) 0.50; 95% CI 0.36–0.65; NRI 0.42; 95% CI 0.33–0.51, respectively]. Conclusion: Serial assessment of hsTnT, NT-proBNP, and GDF-15 revealed that a substantial proportion of patients with AF had dynamic values. Greater increases in these biomarkers measured over 1 year are associated with important clinical outcomes in anticoagulated patients with AF. Graphical Abstract: