Association between adherence to warfarin and thrombotic events in patients with antiphospholipid syndrome in Japan: A claims-based retrospective cohort study

Purpose We aimed to evaluate adherence and persistence to warfarin therapy among patients with antiphospholipid syndrome (APS) and investigate the association between adherence and thrombotic events in those patients. Methods We conducted a retrospective cohort study using the Japan Medical Data Center claims database from 2005 to 2018. Patients with APS receiving warfarin treatment were included in this study. Adherence and persistence were evaluated using the proportion of days covered (PDS) and refill gap methods, respectively. Demographic characteristics of patients were obtained. Kaplan-Meier curves with log-rank tests and Cox regression models were used to examine the association between adherence or persistence and time to thrombotic events. Results A total of 186 patients (mean age: 46.5 +/- 12.4 years, females 68.8%) were included in this study. No significant differences were observed in risk factors for thrombosis and cardiovascular diseases among groups. Most patients were adherent (91.4%) and persistent (88.2%) to warfarin treatment. Adherent and persistent patients had a significantly higher rate of thrombotic event-free survival than nonadherent and nonpersistent patients (p < 0.05). Multivariable Cox regression showed that the risk of thrombotic events was higher in nonadherent patients (with a hazard ratio of 3.23 [95% confidence interval CI: 1.15-9.11]) and in nonpersistent patients (with a hazard ratio of 3.45 [95% CI: 1.35-8.82]). Conclusions In patients with APS, nonadherence and nonpersistence to warfarin treatment was associated with a higher risk of thrombotic events, suggesting the careful monitoring of those patients.