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Objective: Dabigatran and rivaroxaban are novel oral anticoagulants (NOACs) approved for stroke prevention in atrial fibrillation (AF). Although NOACs are more convenient than warfarin, their lack of monitoring may predispose patients to non-persistence. Limited information is available on NOAC non-persistence rates and related clinical outcomes in clinical practice.Methods: We conducted a retrospective cohort study using administrative data from Ontario, Canada, from January 1998 to March 2014 of patients with AF who were dispensed dabigatran or rivaroxaban. Non-persistence was defined as a gap in dabigatran or rivaroxaban prescriptions ≥14 days. A multivariable Cox proportional hazards model was used to estimate the primary composite outcome of stroke, transient ischaemic attack (TIA) and mortality associated with non-persistence.Results: The cohort consisted of 15 857 dabigatran (age 80.7±6.7 year) and 10 119 rivaroxaban users (age 77.0±7.1 year) with women comprising 52% of each medication group. At 6 months, 36.4% of patients were non-persistent to dabigatran, while 31.9% of patients were non-persistent to rivaroxaban. Stroke/TIA/death was significantly higher for those non-persistent to dabigatran (HR 1.76 (95% CI 1.60 to 1.94); p<0.0001) or rivaroxaban (HR 1.89 (95% CI 1.64 to 2.19); p<0.0001) compared with those who were persistent. Risk of stroke/TIA was markedly higher in non-persistent patients to dabigatran (HR 3.75 (95% CI 2.59 to 5.43); p<0.0001) and rivaroxaban (HR 6.25 (95% CI 3.37 to 11.58); p<0.0001) than those persistent.Conclusions: NOAC non-persistence rates are high in clinical practice, with approximately one in three patients becoming non-persistent to dabigatran or rivaroxaban within 6 months after drug initiation. Non-persistence with either dabigatran or rivaroxaban is significantly associated with worse clinical outcomes of stroke/TIA/death. [ABSTRACT FROM AUTHOR]