Anders Nissen Bonde1, Gregory Y H Lip2, Anne-Lise Kamper3, Peter Riis Hansen1, Morten Lamberts1, Kristine Hommel3, Morten Lock Hansen1, Gunnar Hilmar Gislason4, Christian Torp-Pedersen5, Jonas Bjerring Olesen6. 1. Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark. 2. University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom. 3. Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Rigshospitalet, Denmark. 4. Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark; The National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark. 5. Department of Health, Science and Technology, Aalborg University, Aalborg, Denmark. 6. Department of Cardiology, Copenhagen University Hospital Gentofte, Gentofte, Denmark; Department of Cardiology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. Electronic address: anders@nissenbonde.dk.
Abstract
BACKGROUND: The balance between stroke reduction and increased bleeding associated with antithrombotic therapy among patients with atrial fibrillation (AF) and chronic kidney disease (CKD) is controversial. OBJECTIVES: This study assessed the risk associated with CKD in individual CHA₂DS₂-VASc (Congestive heart failure; Hypertension; Age ≥75 years; Diabetes mellitus; previous Stroke, transient ischemic attack, or thromboembolism; Vascular disease; Age 65 to 74 years; Sex category) strata and the net clinical benefit of warfarin in patients with AF and CKD in a nationwide cohort. METHODS: By individual-level linkage of nationwide Danish registries, we identified all patients discharged with nonvalvular AF from 1997 to 2011. The stroke risk associated with non-end-stage CKD and end-stage CKD (e.g., patients on renal replacement therapy [RRT]) was estimated using Cox regression analyses. The net clinical benefit of warfarin was assessed using 4 endpoints: a composite endpoint of death/hospitalization from stroke/bleeding; a composite endpoint of fatal stroke/fatal bleeding; cardiovascular death; and all-cause death. RESULTS: From nonvalvular AF patients (n = 154,259), we identified 11,128 patients (7.2%) with non-end-stage CKD and 1,728 (1.1%) receiving RRT. In all CHA₂DS₂-VASc risk groups, RRT was independently associated with a higher risk of stroke/thromboembolism, from a 5.5-fold higher risk in patients with CHA₂DS₂-VASc score = 0 to a 1.6-fold higher risk in patients with CHA₂DS₂-VASc score ≥2. In patients receiving RRT with CHA₂DS₂-VASc score ≥2, warfarin was associated with lower risk of all-cause death (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.72 to 0.99). In non-end-stage CKD patients with CHA₂DS₂-VASc score ≥2, warfarin was associated with a lower risk of a composite outcome of fatal stroke/fatal bleeding (HR: 0.71, 95% CI: 0.57 to 0.88), a lower risk of cardiovascular death (HR: 0.80, 95% CI: 0.74 to 0.88), and a lower risk of all-cause death (HR: 0.64, 95% CI: 0.60 to 0.69). CONCLUSIONS: CKD is associated with a higher risk of stroke/thromboembolism across stroke risk strata in AF patients. High-risk CKD patients (CHA₂DS₂-VASc ≥2) with AF benefit from warfarin treatment for stroke prevention.
BACKGROUND: The balance between stroke reduction and increased bleeding associated with antithrombotic therapy among patients with atrial fibrillation (AF) and chronic kidney disease (CKD) is controversial. OBJECTIVES: This study assessed the risk associated with CKD in individual CHA₂DS₂-VASc (Congestive heart failure; Hypertension; Age ≥75 years; Diabetes mellitus; previous Stroke, transient ischemic attack, or thromboembolism; Vascular disease; Age 65 to 74 years; Sex category) strata and the net clinical benefit of warfarin in patients with AF and CKD in a nationwide cohort. METHODS: By individual-level linkage of nationwide Danish registries, we identified all patients discharged with nonvalvular AF from 1997 to 2011. The stroke risk associated with non-end-stage CKD and end-stage CKD (e.g., patients on renal replacement therapy [RRT]) was estimated using Cox regression analyses. The net clinical benefit of warfarin was assessed using 4 endpoints: a composite endpoint of death/hospitalization from stroke/bleeding; a composite endpoint of fatal stroke/fatal bleeding; cardiovascular death; and all-cause death. RESULTS: From nonvalvular AFpatients (n = 154,259), we identified 11,128 patients (7.2%) with non-end-stage CKD and 1,728 (1.1%) receiving RRT. In all CHA₂DS₂-VASc risk groups, RRT was independently associated with a higher risk of stroke/thromboembolism, from a 5.5-fold higher risk in patients with CHA₂DS₂-VASc score = 0 to a 1.6-fold higher risk in patients with CHA₂DS₂-VASc score ≥2. In patients receiving RRT with CHA₂DS₂-VASc score ≥2, warfarin was associated with lower risk of all-cause death (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.72 to 0.99). In non-end-stage CKD patients with CHA₂DS₂-VASc score ≥2, warfarin was associated with a lower risk of a composite outcome of fatal stroke/fatal bleeding (HR: 0.71, 95% CI: 0.57 to 0.88), a lower risk of cardiovascular death (HR: 0.80, 95% CI: 0.74 to 0.88), and a lower risk of all-cause death (HR: 0.64, 95% CI: 0.60 to 0.69). CONCLUSIONS: CKD is associated with a higher risk of stroke/thromboembolism across stroke risk strata in AFpatients. High-risk CKD patients (CHA₂DS₂-VASc ≥2) with AF benefit from warfarin treatment for stroke prevention.
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