Chronic Kidney Disease Patients with End-Stage Renal Disease Need Less Warfarin, More Monitoring for Bleeding

Patients who have chronic kidney disease (CKD) and end-stage renal disease (ESRD) require 20% less warfarin and more monitoring for bleeding than patients who have normal kidney function, according to research presented at Kidney Week 2013, the American Society of Nephrology's annual meeting held November 5-10, 2013, in Atlanta, GA.

Despite the increased risk of thromboembolism and bleeding in that patient population, the effect of CKD on warfarin response has not been well studied, and previous published studies suggesting that patients with reduced kidney function require lower warfarin doses included relatively few patients with ESRD. In light of that, Sami Sakaan, PharmD, and colleagues from Methodist University Hospital in Memphis, TN, sought to evaluate the warfarin dosing requirements in patients with stage 3 or higher CKD and compare it to the dosing requirements in patients with normal kidney function.

The authors conducted a retrospective chart review of 225 adult patients to compare the average daily dose of warfarin required to achieve or maintain a therapeutic international normalized ratio (INR) in patients with various degrees of kidney function, to calculate the time required to achieve a therapeutic INR among patients newly initiated on warfarin therapy, and to evaluate adverse effects of bleeding in all groups.

Patients included in the study were continuing or newly initiated to chronic warfarin therapy during their hospitalization with a target INR range of 2 to 3.5 while being dosed by a pharmacy dosing service. Patients were excluded if they were on warfarin for fewer than 4 consecutive days during their hospitalization; if their baseline INR was greater than 1.4; if their hospital admission diagnosis was decompensated congestive heart failure (CHF); if they were hypothyroid or hyperthyroid during their hospitalization; if they were taking selected concomitant medications that significantly affect INR; or if their body mass index (BMI) was greater than 30.

The researchers evaluated warfarin response in hospitalized patients with normal kidney function — defined as glomerular filtration rate >60 mL/min/1.73 m² — and in patients with CKD stage 3 or stage 4/5, or with ESRD initiated or maintained on warfarin for 4 or more consecutive days. Among those groups, the investigators compared the average daily dose to maintain a therapeutic INR, time to achieve that INR in patients newly initiated on warfarin, and adverse effects.

Baseline characteristics, average daily dose, time to therapeutic INR, and other continuous variables were compared and evaluated by using planned contrasts with one-way analysis of variance (ANOVA). Categorical variables were evaluated using contingency tables with chi-square or Fisher’s exact two-tailed test.

Among the patients studied, the average daily dose to maintain a therapeutic INR was statistically lower in CKD patients with ESRD than patients with normal kidney function. In addition, patients with stage 3 or higher CKD experienced significantly more bleeding episodes either during their hospitalization or within 30 days of discharge compared to patients with normal kidney function. However, the median time to reach a therapeutic INR showed no statistical difference among the groups.

The authors concluded that CKD patients with ESRD require less warfarin and more monitoring for bleeding than patients who have normal kidney function.