Quality of anticoagulation control and hemorrhage risk among African American and European American warfarin users

Abstract

Objective We evaluated whether PTTR, risk of over-anticoagulation (INR>4) and risk of hemorrhage differs by race. As PTTR is a strong predictor of hemorrhage risk, we also determined the influence of PTTR on risk of hemorrhage by race. Methods Among 1326 warfarin users, PTTR was calculated as the percentage of interpolated INR values within the target range of 2.0–3.0. PTTR was also categorized as poor (PTTR <60%), good (PTTR≥60<70%), or excellent (PTTR≥70%) anticoagulation control. Over-anticoagulation was defined as INR>4 and major hemorrhages included serious, life threatening and fatal bleeding episodes. Logistic regression and survival analyses were performed to evaluate association of race with PTTR (≥60 vs.<60) and major hemorrhages, respectively. Results Compared to African Americans, European Americans had higher PTTR (57.6% vs. 49.1%; p<0.0001) and were more likely to attain PTTR≥60<70% (22.9% vs. 13.1%; p<0.001) or PTTR≥70% (26.9% vs. 18.2%; p=0.001). Older (>65yrs) patients without venous thromboembolism indication and chronic kidney disease were more likely to attain PTTR≥60%. After accounting for clinical and genetic factors, and PTTR, African Americans had a higher risk of hemorrhage (HR: 1.58; 95%CI 1.04–2.41; p=0.034). Patients with PTTR≥60<70% (HR 0.62; 0.38–1.02; p=0.058) and PTTR≥70% (HR 0.27; 0.15–0.49; p<0.001) had a lower risk of hemorrhage compared to those with PTTR<60%. Conclusion Despite provision of warfarin management through anticoagulation clinics, African Americans achieve a lower overall PTTR and have a significantly higher risk of hemorrhage. Personalized medicine interventions tailored to the African American warfarin users need to be developed.

Influence of Age on Warfarin Dose, Anticoagulation Control, and Risk of Hemorrhage

“…We also evaluated the differential effect of self-reported race on warfarin, reporting on the variable effect of genetic and nongenetic factors on warfarin dose and hemorrhage by race. 28,36 However, the effect of age on warfarin dose was similar across race groups in our study. 28 Age is also an important predictor of bleeding outcomes among warfarin users and has been incorporated into several bleeding risk scores.…”

“…Our own research group has previously reported on the associations of kidney function, left ventricular systolic dysfunction, and the CYP2C9 , VKORC1 , and CYP4F2 variants with warfarin dose. We also evaluated the differential effect of self‐reported race on warfarin, reporting on the variable effect of genetic and nongenetic factors on warfarin dose and hemorrhage by race . However, the effect of age on warfarin dose was similar across race groups in our study …”

“…All complications were adjudicated independently by the medical director of the Anticoagulation Clinic. Only medically documented adjudicated events were included in the analyses, as previously reported …”

“…Only medically documented adjudicated events were included in the analyses, as previously reported. 27,[36][37][38] Statistical Analyses Analysis of variance was used to assess group differences for continuous variables and v 2 for categorical variables. All SNPs were tested for the Hardy-Weinberg equilibrium assumption by calculating the allele as well as genotype frequencies and using a v 2 exact test.…”

Evaluation of the Validity of SAMe-TT2R2 Score in a Cohort of Venous Thromboembolism Patients Treated With Warfarin

“…Moreover, they experienced significantly lower bleeding episodes (Incidence rate ratio: 1.38, 95% CI: 1.01, 1.89, P = .045) and were at significantly lower relative risk of major hemorrhagic events (HR: 1.58; 95% CI: 1.04-2.41; P = .03) despite adjusting for clinical and genetic factors and TTR. 30 In the study of Kataruka et al, 21 none of the score’s factors was independently associated with predicting poor anticoagulation control. Analysis identified weight, history of previous VTE, and alcohol consumption, which are risk factors not included in the SAMe-TT 2 R 2 score, as significant predictors of low TTR (<60%).…”