Abstract 16445: Anticoagulation Control, Risk of Overanticoagulation and Major Hemorrhage Among Warfarin Users is Influenced by Race

Abstract

Objective: Racial differences in warfarin response have been of significant interest. Differences in dose requirements have been extensively studied. Herein, we assess whether anticoagulation control [percent time in target range (PTTR; INR range 2-3)], risk of overanticoagulation (INR>4) and major hemorrhage differ by race among warfarin users. Methods: The analysis included 1357 participants [595 African Americans (AA); 762 European Americans (EA)]. The Rosendaal interpolation method was used to compute the PTTR, percent time above range (PTAR) and percent time below range (PTBR). Major hemorrhages included serious, life threatening and fatal bleeding events. The influence of race (AA vs. EA) on PTTR, PTBR, and PBAR was evaluated using linear regression; overanticoagulation and hemorrhage by Cox proportional hazards analysis adjusting for clinical and genetic factors. Results: Over 1912 person-years (pyrs) accrued (average per patient 1.4 (± 0.9) years), after adjusting for covariates, compared to EAs, AAs had lower PTTR (56.3% vs. 50.8% p<0.001), higher PTBR (26.5% vs. 31.2%; p=0.001) and were also more likely to experience overanticoagulation (HR: 1.31, 95% CI 1.10-1.56, p=0.003). A total of 156 major hemorrhagic events were encountered (incidence 8.2/100 pyrs, 95% CI: 7.0 – 9.5/100 pyrs). AAs had higher incidence of hemorrhage compared to EAs (IRR: 1.38, 95% CI 1.00-1.89, p=0.046). After adjusting for clinical and genetic factors, AAs remained at a higher risk for hemorrhage (HR: 1.60, 95% CI: 1.10-2.34, p=0.016). Older age, antiplatelet therapy, renal impairment, and possession of CYP2C9 variants increased the risk of hemorrhage. Higher PTTR was associated with a lower risk of hemorrhage in both race groups. Compared to patients with PTTR<50%; those with PTTR 50-60% had a 37% lower risk (HR=0.63; 95%CI0.4-0.97; p=0.04), those with PTTR 60-70% had a 43% lower risk (HR=0.57; 95%CI 0.35-0.92; p=0.02), and those with PTTR >70 had a 75% lower risk (HR=0.25; 95%CI0.14-0.43; p<0.0001). Conclusion and Relevance: Among warfarin users, African Americans spent less time in target INR range, and had a higher risk of overanticoagulation and hemorrhage. Strategies to improve anticoagulation control among African Americans can lower risk of hemorrhage.