Key result
CKD and ESRD linked to ~20% lower daily warfarin doses to maintain therapeutic INR.
Why the study?
Patients with reduced kidney function may require lower warfarin doses and face increased thromboembolism and bleeding risks, yet relatively few patients with end-stage renal disease were included in previous studies.
Does chronic kidney disease and ESRD reduce warfarin dose requirements and time to therapeutic INR compared to normal kidney function in hospitalized adults?
Cohort (n=210)
Does chronic kidney disease and ESRD reduce warfarin dose requirements and time to therapeutic INR compared to normal kidney function in hospitalized adults?
Patients with CKD and ESRD require approximately 20% lower warfarin doses and less time to achieve a therapeutic INR compared to patients with normal kidney function.
Answers are grounded in this paper and cite their sources.
Supports lower initial warfarin dosing in CKD/ESRD; hypothesis-generating and requires prospective validation before practice change.
Study Objectives The effect of chronic kidney disease (CKD) on warfarin has gained attention because of an increased risk of thromboembolism and an increased risk of bleeding associated with warfarin treatment in these patients. Data suggest that patients with reduced kidney function require lower warfarin doses; however, relatively few patients with end‐stage renal disease (ESRD) were included in previous studies. The goal of this study was to evaluate warfarin dosing requirements and time to reach therapeutic international normalized ratio (INR) in patients with CKD stages 3–5 and ESRD compared with patients with normal kidney function (NKF). Methods A historical cohort was identified to evaluate warfarin response in 210 hospitalized adults with varying degrees of kidney function initiated or maintained on warfarin for 4 or more consecutive days including 49 patients with NKF (glomerular filtration rate [GFR] higher than 60 ml/min/1.73 m2), 44 with CKD stage 3, 27 with CKD stage 4/5, and 90 with ESRD. The average daily dose (ADD), time to achieve a therapeutic INR, and adverse effects were compared. Measurements and Main Results The ADD to maintain a therapeutic INR was 5.6 ± 1.7 mg in the NKF group, 4.3 ± 1.6 mg in CKD stage 3, 4.6 ± 1.9 mg in CKD stage 4/5, and 4.8 ± 1.9 mg in ESRD. The ADD was lower in CKD/ESRD patients compared with NKF patients (p=0.001), especially among whites. The time to reach a therapeutic INR in patients newly initiated on warfarin was significantly lower in the CKD/ESRD group when compared with the NKF group (p=0.02). No differences in bleeding episodes were observed during hospitalization or within 30 days of discharge in patients with CKD stage 3 or higher compared with patients with NKF. Conclusions Our findings suggest that CKD and ESRD patients require ~20% lower warfarin doses to maintain a therapeutic INR and may require less time to achieve a therapeutic INR compared with patients with NKF.
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Sakaan et al. (2014) conducted a cohort in Chronic kidney disease (CKD stages 3-5) and end-stage renal disease (ESRD) on warfarin (n=210). Chronic kidney disease (stages 3-5) and end-stage renal disease on warfarin vs. Normal kidney function (GFR >60 ml/min/1.73 m2) on warfarin was evaluated on Average daily dose (ADD) of warfarin to maintain a therapeutic INR (p=0.001). CKD and ESRD patients required ~20% lower average daily warfarin doses to maintain a therapeutic INR compared with normal kidney function patients (4.3-4.8 mg vs 5.6 mg; p=0.001).
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