P4768Comparative effectiveness and safety between non-VKA oral anticoagulants in non-valvular atrial fibrillation patients with differential duration of treatment: an analysis of the ARISTOPHANES study
Authors: Deitelzweig S , Keshishian A , Kang A , Dhamane A , Luo X , Li X , Balachander N , Rosenblatt L , Mardekian J , Jiang J , Di Fusco M , B Garcia Reeves A , Yuce H , Lip G Y H 
Published: October 2019

Abstract

Background
The ARISTOPHANES (Anticoagulants for Reduction In STroke: Observational Pooled analysis on Health outcomes ANd Experience of patientS) study showed that apixaban was associated with lower risks of stroke/systemic embolism (S/SE) and major bleeding (MB) versus dabigatran and rivaroxaban; dabigatran was associated with similar risk of S/SE and lower risk of MB compared to rivaroxaban.

Purpose
To assess long-term use of non-VKA oral anticoagulants (NOACs) in ARISTOPHANES by evaluating the risk of S/SE and MB among non-valvular atrial fibrillation (NVAF) patients receiving different NOACs by duration of treatment (<1 and ≥1 year).

Methods
In the ARISTOPHANES study, NVAF patients initiating apixaban, dabigatran, and rivaroxaban from 01/01/2013–09/30/2015 were identified from the CMS Medicare data and four US commercial claims databases, covering >180 million beneficiaries annually (∼56% of US population). After 1:1 propensity score matching (PSM) in each database between NOACs (apixaban-dabigatran, apixaban-dabigatran, and dabigatran-rivaroxaban), the resulting patient records were pooled. Treatment duration was defined as time between the day after the index treatment date and discontinuation (defined using a 30-day gap in the prescription), treatment switch, death, end of study period, or end of continuous medical and pharmacy enrollment, whichever occurred first. Matched patients with observed treatment duration <1 or ≥1 year were separately examined. Cox models were used to estimate hazard ratios of S/SE and MB (identified by inpatient claims) during observed treatment duration. S/SE included ischemic stroke, hemorrhagic stroke, and SE; MB included gastrointestinal (GI) bleeding, intracranial hemorrhage (ICH), and other MB.

Results
The mean treatment duration for patients with shorter (<1 year) vs longer (≥1 year) duration was ∼4 months vs 18–21 months across the three matched cohorts. All the matched baseline variables remained balanced. The incidence rates of S/SE and MB and the proportion of patients with treatment discontinuation were higher in patients with shorter treatment duration. Regardless of treatment duration, apixaban and dabigatran had a lower risk of MB versus rivaroxaban; and dabigatran had a similar risk of S/SE versus rivaroxaban. Compared to dabigatran patients, apixaban patients with treatment duration <1 year had a lower risk of S/SE and MB, while those with treatment duration ≥1 year had similar S/SE and MB risk. Compared to rivaroxaban patients, apixaban patients with treatment duration <1 year had a lower risk of S/SE, while those with treatment duration ≥1 year had similar S/SE risk.

Conclusions
Across NVAF patients with duration of treatment <1 and ≥1 year in the ARISTOPHANES study, both apixaban and dabigatran were associated with a lower risk of MB compared to rivaroxaban. These findings indicate varying long-term safety outcomes among different NOACs.

Acknowledgement/Funding
This study was funded by Bristol-Myers Squibb and Pfizer Inc.