Pillbox use and INR stability in a prospective cohort of new warfarin users

Abstract

BACKGROUND: Warfarin, a frequently prescribed oral anticoagulant, is well known for its narrow therapeutic index. Adherence to warfarin may help to achieve a stable international normalized ratio (INR), but little data are available regarding the impact of using a pillbox as a potential adherence aid device. OBJECTIVE: To evaluate the association between pillbox use and time in therapeutic range (TTR) < 60[%] and INR instability pattern. METHODS: This study was based on a prospective cohort of 1,069 new warfarin users who initiated warfarin between May 2010 and July 2013 within 17 hospitals in Quebec, Canada. Demographic, lifestyle, and clinical data were collected for 3 months to a year after warfarin initiation, and genetic factors were assessed. Patients usingh self-prepared and pharmacist-prepared pillboxes were compared with nonusers for the 3- to 12-month follow-up period. The primary outcome was a TTR < 60[%], which represents a low percentage of time in the INR therapeutic range or an unstable patient. The secondary outcome was the INR instability pattern (unstable below range; unstable over range; unstable with erratic pattern; and stable) to better describe patient INR profiles. A multivariate generalized linear mixed model was used for the primary outcome, along with a multivariate multinomial linear mixed model for the secondary outcome. RESULTS: The cohort included patients with a mean age of 70.4 ± 11.7 years; 61.8[%] of patients were men; 76.3[%] had atrial fibrillation as warfarin's primary indication; and 35.6[%] had a previous history of myocardial infarction or angina. Self-prepared and pharmacist-prepared pillbox use was not associated with TTR < 60[%] or a specific INR instability pattern. A sensitivity analysis showed that self-prepared pillbox users had a higher TTR than nonusers (3.55[%] ± 1.69[%]; P = 0.036). This effect was greater among patients aged < 70 years (5.48[%] ± 2.50[%]; P = 0.029) than among older patients (1.92[%] ± 2.31[%]; P = 0.406). CONCLUSIONS: Pillbox use was not associated with TTR < 60[%] or a specific INR instability pattern. The impact of self-prepared pillbox use was greater among younger patients, but results were not clinically significant. Future studies adjusting for concomitant drug use are needed to clarify these results.