Megan V Yanik1, Marguerite R Irvin2, T Mark Beasley3, Pamala A Jacobson4, Bruce A Julian5, Nita A Limdi6. 1. Division of Nephrology, Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama. 2. Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama. 3. Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, Alabama. 4. Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota. 5. Division of Nephrology, Medicine, University of Alabama at Birmingham, Birmingham, Alabama. 6. Neurology, University of Alabama at Birmingham, Birmingham, Alabama.
Abstract
STUDY DESIGN: To assess whether warfarin dose requirement, anticoagulation control, and risk of hemorrhage differ in kidney transplant recipients (KTRs) compared with patients without kidney transplants (non-KTRs). DESIGN: Analysis of data from the Warfarin Pharmacogenetics Cohort, a prospective cohort of first-time warfarin users followed at two anticoagulation clinics. SETTING: Two outpatient anticoagulation clinics at two large, academic, tertiary care hospitals. PATIENTS: Adults aged 20 years or older starting warfarin for anticoagulation with a therapeutic international normalized ratio (INR) goal of 2-3 who were KTRs (n=65) or non-KTRs (n=1630). MEASUREMENTS AND MAIN RESULTS: Warfarin dose requirement, anticoagulation control, and risk of hemorrhage were assessed in each group. KTRs required an approximately 20% lower warfarin dose (4.7 vs 5.6 mg/day, p=0.0005) compared with non-KTRs. Genetic variants had similar effects on dose in both groups. Mean percentage of time in therapeutic range (PTTR) was similar among KTRs and non-KTRs. Although the proportion of patients achieving good anticoagulation control (PTTR ≥ 60%) was low in both groups, it was similar among KTRs and non-KTRs. KTRs had a higher risk of major hemorrhage (hazard ratio 2.1, p=0.0081), but this difference was not statistically significant after controlling for kidney function, clinical, and genetic factors. CONCLUSION: KTRs initiating warfarin require lower doses and closer monitoring to optimize anticoagulation therapy. Additional studies are needed to confirm these findings.
STUDY DESIGN: To assess whether warfarin dose requirement, anticoagulation control, and risk of hemorrhage differ in kidney transplant recipients (KTRs) compared with patients without kidney transplants (non-KTRs). DESIGN: Analysis of data from the Warfarin Pharmacogenetics Cohort, a prospective cohort of first-time warfarin users followed at two anticoagulation clinics. SETTING: Two outpatient anticoagulation clinics at two large, academic, tertiary care hospitals. PATIENTS: Adults aged 20 years or older starting warfarin for anticoagulation with a therapeutic international normalized ratio (INR) goal of 2-3 who were KTRs (n=65) or non-KTRs (n=1630). MEASUREMENTS AND MAIN RESULTS:Warfarin dose requirement, anticoagulation control, and risk of hemorrhage were assessed in each group. KTRs required an approximately 20% lower warfarin dose (4.7 vs 5.6 mg/day, p=0.0005) compared with non-KTRs. Genetic variants had similar effects on dose in both groups. Mean percentage of time in therapeutic range (PTTR) was similar among KTRs and non-KTRs. Although the proportion of patients achieving good anticoagulation control (PTTR ≥ 60%) was low in both groups, it was similar among KTRs and non-KTRs. KTRs had a higher risk of major hemorrhage (hazard ratio 2.1, p=0.0081), but this difference was not statistically significant after controlling for kidney function, clinical, and genetic factors. CONCLUSION: KTRs initiating warfarin require lower doses and closer monitoring to optimize anticoagulation therapy. Additional studies are needed to confirm these findings.
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