March 1, 2022Scientific ReportsOpen Access

Adherence is an optimal factor for maximizing the effective and safe use of oral anticoagulants in patients with atrial fibrillation

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Why the study?

Few studies had evaluated the association between major adverse cardiovascular events and adherence to warfarin versus DOACs in patients with atrial fibrillation.

Does adherent use of oral anticoagulants reduce the risk of ischemic stroke, myocardial infarction, and death in patients with atrial fibrillation compared to non-adherent use?

Structured PICO

Does adherent use of oral anticoagulants reduce the risk of ischemic stroke, myocardial infarction, and death in patients with atrial fibrillation compared to non-adherent use?

Population

67,147 newly treated adult patients with non-valvular atrial fibrillation taking oral anticoagulants (males with CHA2DS2-VASc ≥ 2, females with CHA2DS2-VASc ≥ 3), South Korean claims data.

Intervention

Adherent use of oral anticoagulants (warfarin or DOACs including rivaroxaban, apixaban, dabigatran, and edoxaban), defined as a medication possession rate (MPR) ≥ 0.8 during the initial 3 months.

Comparator

Non-adherent use of oral anticoagulants (MPR < 0.8 during the initial 3 months), propensity score matched (1:1 for warfarin, 1:3 for DOACs).

Outcome

Incidence of ischemic stroke, myocardial infarction (MI), intracranial hemorrhage, and all-cause death assessed independently.hard clinical

Adherence to direct oral anticoagulants in patients with atrial fibrillation significantly reduces the risk of ischemic stroke, myocardial infarction, and all-cause death without increasing the risk of intracranial hemorrhage.

Limitations

Adherence was estimated by prescription days using claims data, which cannot capture if patients actually took the dispensed medication.
Potential misclassification bias due to the use of diagnostic codes from claims data.
The protective effect of adherence might have been overestimated as the adherent group was older and had a slightly greater disease burden.
Did not observe statin use, which may affect cardiovascular events.
Adherence is a time-varying covariate, though simplified using initial 3-month MPR.

Implication

May support adherence promotion in AF on DOACs; hypothesis-generating and requires RCT confirmation.

Abstract

Few studies assessed the association between major adverse cardiovascular events and adherence to warfarin and direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF). Therefore, we aimed to evaluate the effects of adherence to oral anticoagulants (OACs) in patients with AF using claims data (July 2014-April 2019). Using the initial 3-month medication possession rate (MPR), patients were categorized into adherent (MPR ≥ 0.8) or non-adherent (MPR < 0.8) groups. Propensity score matching of non-adherent group to adherent group was conducted for warfarin (1:1) and DOAC (1:3), respectively. Incidence of ischemic stroke, myocardial infarction (MI), intracranial hemorrhage, and all-cause death was assessed in the matched cohort (67,147 patients). The hazard ratio (HR) for adherence to OAC was estimated using the Cox proportional hazard model with adjusting covariate including age and sex. The risk for ischemic stroke, MI, and all-cause death was lower in the DOAC adherent group than in the DOAC non-adherent group (HR: 0.78; 95% confidence intervals: 0.73-0.84; 0.75, 0.60-0.94; 0.54, 0.51-0.57, respectively). Adherence to OAC was not associated with the risk of intracranial hemorrhage (1.01, 0.85-1.20). Commitment programs to improve adherence in patients with AF could maximize drug effectiveness and safety.