Warfarin management and outcomes in patients with nonvalvular atrial fibrillation within an integrated health care system

Abstract

BACKGROUND: Warfarin is a common treatment option to manage patients with nonvalvular atrial fibrillation (NVAF) in clinical practice. Understanding current pharmacist-led anticoagulation clinic management patterns and associated outcomes is important for quality improvement; however, currently little evidence associating outcomes with management patterns exists. OBJECTIVES: To (a) describe warfarin management patterns and (b) evaluate associations between warfarin treatment and clinical outcomes for patients with NVAF in an integrated health care system. METHODS: A retrospective cohort study was conducted among NVAF patients with warfarin therapy between January 1, 2006, and December 31, 2011, using Kaiser Permanente Southern California data, and followed until December 31, 2013. Management patterns related to international normalized ratio (INR) monitoring, anticoagulation clinic pharmacist intervention (consultation), and warfarin dose adjustments were investigated along with yearly attrition rates, time-in-therapeutic ranges (TTRs), and clinical outcomes (stroke or systemic embolism and major bleeding). Descriptive statistics and multivariable Cox proportional hazard models were used to determine associations between TTR and clinical outcomes. RESULTS: A total of 32,074 NVAF patients on warfarin treatment were identified and followed for a median of 3.8 years. About half (49[%]) of the patients were newly initiating warfarin therapy. INR monitoring and pharmacist interventions were conducted roughly every 3 weeks after 6 months of warfarin treatment. Sixty-three percent of the study population had > 1 warfarin dose adjustments with a mean (SD) of 6.7 (6.3) annual dose adjustments. Warfarin dose adjustments occurred at a median of 1 day (interquartile ranges [[]IQR] 1-3) after the INR measurement. Yearly attrition rate was from 3.3[%] to 6.3[%] during the follow-up, and median (IQR) TTR was 61[%] (46[%]- 73[%]). Patients who received frequent INR monitoring (> 27 times per year), pharmacist interventions (> 24 times per year), or frequently adjusted warfarin dose (> 11 times per year) consistently showed poor TTRs (mean TTR for the highest quartiles was 45.3[%]-48.3[%]). A higher TTR was associated with a lower risk of clinical outcomes regardless of frequency of INR monitoring, pharmacist interventions, or number of dose adjustments. Patients whose TTRs were < 65[%], even with frequent pharmacist interventions, had similar stroke or systemic embolism event rates, as compared with patients with TTRs < 65[%] and less frequent interventions (1.88 vs. 1.54 stroke or systemic embolism rates per 100 person-years, respectively, P = 0.78). The lowest TTR quartile (< 46[%]) was associated with a 3 times higher risk of stroke or systemic embolism (hazard ratio [[]HR] = 3.19, 95[%] CI = 2.71-3.77) and a 2 times higher risk of major bleeding (HR=2.10, 95[%] CI = 1.96-2.24) compared with the highest TTR quartile (> 73[%]). CONCLUSIONS: Despite close monitoring with timely warfarin dose adjustments, there were still a substantial number of challenging patients whose TTRs were suboptimal despite a higher number of pharmacist interventions. These patients eventually experienced more stroke or systemic embolism and bleeding events among NVAF patients managed by anticoagulation clinics. New individualized treatment or management strategies for patients who are not able to reach optimal therapeutic ranges are nec essary to improve outcomes.