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Effect of Kidney Transplant Status on Warfarin Management and Bleeding Risk
Study Questions:
For kidney transplant recipients (versus patients without kidney transplants), does warfarin dosing, anticoagulation management, and hemorrhagic risk differ?
Methods:
This is a prospective cohort of patients new to warfarin therapy followed at anticoagulation clinics using data from the Warfarin Pharmacogenetics Cohort. Kidney transplant patients and patients with chronic kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m2) ≥20 years old were included. Other inclusion criteria were international normalized ratio (INR) goal range of 2-3 with indications for warfarin including venous thromboembolism (VTE), atrial fibrillation, stroke, and myocardial infarction.
Results:
A total of 65 kidney transplant recipients and 1,630 patients without kidney transplants was included. For the kidney transplant group, patients more commonly had history of hypertension (80 vs. 67%, p = 0.029), were more commonly prescribed warfarin for VTE prevention (63.1 vs. 43.1%, p = 0.004), and were younger (53.8 vs. 61.6 years, p < 0.001) than the non-transplant group. The kidney transplant recipients were also more often on statins (80 vs. 54.7%, p < 0.001) and taking amiodarone (20 vs. 9.9%, p = 0.018). The warfarin doses needed to keep INRs in goal range of 2-3 (4.7 vs. 5.6 mg/day, p = 0.005) and time needed to achieve goal range (13.5 vs. 19.2 days, p = 0.033) were lower for kidney transplant recipients. INRs were checked more frequently for kidney transplant recipients (2.74 vs. 2.26 visits/patients/month, p < 0.005). Percent time in therapeutic range was not different between groups. Percent time in therapeutic range was reduced (<60%) in both groups (72.3% kidney transplant recipients vs. 62.8% patients without kidney transplants) and not significantly different. Adjusting for clinical, genetic, and demographic variables, there was no difference between groups in risk of INR > 4 (hazard ratio 1.4; 95% confidence interval, 0.94-2.0; p = 0.11). Kidney transplant recipients were found to have a higher risk of major hemorrhage (hazard ratio 2.1; 95% confidence interval, 1.2-3.8; p = 0.008). Taking into account renal function and genetic and clinical factors, however, this was no longer statistically significant (hazard ratio 1.22; 95% confidence interval, 0.73-2.84; p = 0.29).
Conclusions:
When initiating warfarin in kidney transplant recipients, lower initial doses and closer monitoring may be needed. Although increased rates of major hemorrhage were seen in kidney transplant recipients, this was not found to be significantly different from patients without kidney transplants when adjusting for relevant variables. Further studies are needed to understand the benefit of warfarin and risk of thrombotic and hemorrhagic events in kidney transplant recipients.
Perspective:
Kidney transplant recipients on warfarin required a dose almost 20% lower than patients without kidney transplants and achieved a therapeutic INR (2-3) more quickly. It is important to consider a lower initial dose and more frequent monitoring in these patients to achieve good percent time in therapeutic range and to avoid adverse events from sub- or supra-therapeutic INRs.
Keywords: Kidney Transplantation, Warfarin, Renal Insufficiency, Chronic, Hemorrhage, Hydroxymethylglutaryl-CoA Reductase Inhibitors, International Normalized Ratio, Amiodarone, Glomerular Filtration Rate, Myocardial Infarction, Stroke, Hypertension
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