Net Clinical Benefit of Antithrombotic Therapy in Patients With Atrial Fibrillation and Chronic Kidney Disease: A Nationwide Observational Cohort Study
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.
Key Words
arrhythmia
atrial fibrillation
CHA2DS2-VASc score
chronic kidney disease
thromboprophylaxis
warfarin
Abbreviations and Acronyms
AF
atrial fibrillation
CI
confidence interval
CKD
chronic kidney disease
HR
hazard ratio
ICD
International Classification of Diseases
IQR
interquartile range
RRT
renal replacement therapy
TE
thromboembolism
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The Capital Region of Denmark, Foundation for Health Research has financed this study through a research grant for Dr. Jonas Bjerring Olesen. Dr. Lip has served as a consultant for Bayer Healthcare, Astellas, Merck & Co., Inc., Sanofi, BMS/Pfizer, Daiichi-Sankyo, Biotronik, Medtronic, Portola, AstraZeneca, and Boehringher Ingelheim; and has served on the speakers bureaus for Bayer Healthcare, BMS/Pfizer, Boehringher Ingelheim, Daiichi-Sankyo, Medtronic, and Sanofi. Dr. Gislason has received research grants and speaking fees from AstraZeneca and Bristol-Myers Squibb. Dr. Torp-Pedersen has developed antiarrhythmic drugs; and has received fees for lecturing, serving on advisory boards, and steering committees for Cardiome, Sanofi, and Merck & Co., Inc. Dr. Bjerring Olesen has received speaking fees from Bristol-Myers Squibb; and funding for research from the Lundbeck Foundation, Bristol-Myers Squibb, and The Capital Region of Denmark, Foundation for Health Research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.