OBJECTIVES. Observational studies have examined the direct oral anticoagulant (DOACs) dosage used in non-valvular atrial fibrillation (NVAF). Studies reported that a greater proportion received low dose DOACs in contrast to RCT. Comparative effectiveness and safety of low dose DOACs to warfarin in NVAF patients need to be addressed. To assess comparative effectiveness and safety of low dose DOACs to warfarin and apixaban.

METHODS. We built a cohort using Quebec administrative databases (Med-Echo and RAMQ) from 2011 to 2018 in NVAF patients hospitalized and discharged in the community. Cohort entry was defined as the first OAC claim in new users, defined as no OAC claims in 1-year prior. We determined patient demographics, comorbidities, CHA₂DS₂-VASc score and HASBLED for 3-year prior to cohort entry. Medication use was documented 2 weeks prior to cohort entry. Effectiveness outcomes (ischemic stroke/systemic thrombosis, myocardial infarction, death, composite) and safety outcomes (intracranial bleeding, extracranial major bleeding, composite) were assessed at 1-year follow-up or censoring. We conducted a propensity score matched population and hazard ratios (HRs) for outcomes were estimated using Cox proportional hazard models. Several sensitivity analyses were performed.

RESULTS. The cohort consisted of 22,969 incident OAC new users aged between 80-86 years. Comparative effectiveness and safety outcomes of low dose dabigatran and rivaroxaban relative to warfarin suggested that there was no significant difference. Although, low dose apixaban presented a better safety profile with risk reduction for ICH (HR: 0.66; 95%CI 0.43-0.99), extracranial bleeding (HR: 58; 0.40-0.84), and safety composite (HR: 0.61; 0.46-0.81). For relative comparisons of dabigatran or rivaroxaban to apixaban, no significant difference for the effectiveness outcomes but an increasing risk of major bleeding.

CONCLUSIONS.

Almost half of patients in our cohort were treated with low dose DOAC. The effectiveness does not seem to vary across OAC but apixaban had a better safety profile.