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

• Type of Material: Article
• Authors: Nita A. Limdi, University of Alabama Birmingham; Todd M. Brown, University of Alabama Birmingham; Aditi Shendre, University of Alabama Birmingham; Nianjun Liu, University of Alabama Birmingham; Charles Hill, Emory University; T. Mark Beasley, University of Alabama Birmingham
• Language: English
• Date: 2017-10-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Wolters Kluwer Health, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1097/FPC.0000000000000298
• Title of Journal or Parent Work: Pharmacogenetics and Genomics
• ISSN: 1744-6872
• Volume: 27
• Issue: 10
• Start Page: 347
• End Page: 355
• Grant/Funding Information: This work was supported in part by grants from the National Heart Lung and Blood Institute (RO1HL092173; 1K24HL133373), National Institute of General Medical Sciences (R01GM081488) and the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program (UL1TR000165).
• Keywords: RE-LY TRIAL; THERAPEUTIC RANGE; Biotechnology & Applied Microbiology; percent time in target range; KIDNEY-FUNCTION; anticoagulation control; Science & Technology; STROKE PREVENTION; GENOTYPE; CLINICAL-TRIALS; race; hemorrhage; Genetics & Heredity; NORMALIZED RATIO CONTROL; Pharmacology & Pharmacy; Life Sciences & Biomedicine; warfarin; ORAL ANTICOAGULATION; RANDOMIZED CONTROLLED-TRIAL; ATRIAL-FIBRILLATION
• Research Categories: Health Sciences, Pharmacology; Biology, Microbiology

Abstract

Objective We evaluated whether percent time in target range (PTTR), risk of over-Anticoagulation [international normalized ratio (INR)>4], and risk of hemorrhage differ by race. As PTTR is a strong predictor of hemorrhage risk, we also determined the influence of PTTR on the risk of hemorrhage by race. Participants and 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 (60≤PTTR<70%), or excellent (PTTR≥70%) anticoagulation control. Over-Anticoagulation was defined as INR more than 4 and major hemorrhages included serious, life-Threatening, and fatal bleeding episodes. Logistic regression and survival analyses were carried out to evaluate the association of race with PTTR (≥60 vs. <60) and major hemorrhages, respectively. Results Compared with African Americans, European Americans had higher PTTR (57.6 vs. 49.1%; P<0.0001) and were more likely to attain 60≤PTTR<70% (22.9 vs. 13.1%; P<0.001) or PTTR of at least 70% (26.9 vs. 18.2%; P=0.001). Older (>65 years) patients without venous thromboembolism indication and chronic kidney disease were more likely to attain PTTR of at least 60%. After accounting for clinical and genetic factors, and PTTR, African Americans had a higher risk of hemorrhage [hazard ratio (HR)=1.58; 95% confidence interval (CI): 1.04-2.41; P=0.034]. Patients with 60≤PTTR<70% (HR=0.62; 95% CI: 0.38-1.02; P=0.058) and PTTR of at least 70% (HR=0.27; 95% CI: 0.15-0.49; P<0.001) had a lower risk of hemorrhage compared with those with PTTR less than 60%. Conclusion Despite the 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 African American warfarin users need to be developed.