Gerald Chi1, James L Januzzi2, Serge Korjian1, Yazan Daaboul1, Samuel Z Goldhaber3, Adrian F Hernandez4, Russell D Hull5, Alex Gold6, Alexander T Cohen7, Robert A Harrington8, C Michael Gibson9. 1. PERFUSE Study Group, Cardiovascular Division, Departments of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Suite OV-540, Boston, MA, USA. 2. Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 3. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 4. Duke University and Duke Clinical Research Institute, Durham, NC, USA. 5. Division of Cardiology, R.A.H Faculty of Medicine, University of Calgary, Alberta, Canada. 6. Portola Pharmaceuticals Inc., South San Francisco, CA, USA. 7. Department of Haematological Medicine, Guy's and St Thomas' Hospitals, King's College, London, UK. 8. Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, CA, USA. 9. PERFUSE Study Group, Cardiovascular Division, Departments of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Suite OV-540, Boston, MA, USA. mgibson@perfuse.org.
Abstract
BACKGROUND: Among patients hospitalized with acute heart failure (HF), the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in short-term stroke prediction remains unclear. METHODS: In the APEX trial, 7513 patients hospitalized for an acute medical illness were randomized to receive either extended-duration betrixaban (80 mg once daily for 35-42 days) or standard-of-care enoxaparin (40 mg once daily for 10 ± 4 days) for venous thromboprophylaxis. Baseline NT-proBNP concentrations were obtained in 3261 patients admitted for HF. Stroke events were adjudicated by an independent clinical events committee blinded to thromboprophylaxis allocation. The association of NT-proBNP level and other risk factors and biomarkers with stroke was assessed at 77 days after randomization. RESULTS: In univariate analysis, the risk of stroke at 77 days was associated with baseline NT-proBNP (HR 3.63 [95% CI 1.47-8.99]; P = 0.005), D-dimer (HR 2.73 [95% CI 1.03-7.20]; P = 0.043), and hsCRP (HR 3.03 [95% CI 1.36-6.75]; P = 0.007). In multivariable analysis adjusting for hsCRP and thromboprophylaxis, NT-proBNP was associated with the risk of stroke (adjusted HR 3.64 [95% CI 1.35-9.83]; P = 0.011). The interaction of NT-proBNP with the treatment effect was not significant (Pint = 0.30). CONCLUSIONS:Baseline NT-proBNP concentration was associated with short-term stroke among patients hospitalized with acute HF. Stroke risk assessment models should consider incorporation of NT-proBNP measurement.
RCT Entities:
BACKGROUND: Among patients hospitalized with acute heart failure (HF), the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in short-term stroke prediction remains unclear. METHODS: In the APEX trial, 7513 patients hospitalized for an acute medical illness were randomized to receive either extended-duration betrixaban (80 mg once daily for 35-42 days) or standard-of-care enoxaparin (40 mg once daily for 10 ± 4 days) for venous thromboprophylaxis. Baseline NT-proBNP concentrations were obtained in 3261 patients admitted for HF. Stroke events were adjudicated by an independent clinical events committee blinded to thromboprophylaxis allocation. The association of NT-proBNP level and other risk factors and biomarkers with stroke was assessed at 77 days after randomization. RESULTS: In univariate analysis, the risk of stroke at 77 days was associated with baseline NT-proBNP (HR 3.63 [95% CI 1.47-8.99]; P = 0.005), D-dimer (HR 2.73 [95% CI 1.03-7.20]; P = 0.043), and hsCRP (HR 3.03 [95% CI 1.36-6.75]; P = 0.007). In multivariable analysis adjusting for hsCRP and thromboprophylaxis, NT-proBNP was associated with the risk of stroke (adjusted HR 3.64 [95% CI 1.35-9.83]; P = 0.011). The interaction of NT-proBNP with the treatment effect was not significant (Pint = 0.30). CONCLUSIONS: Baseline NT-proBNP concentration was associated with short-term stroke among patients hospitalized with acute HF. Stroke risk assessment models should consider incorporation of NT-proBNP measurement.
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