Using Real-world Data to Assess Comparative Effectiveness and Safety of Apixaban and Rivaroxaban in Patients with Nonvalvular Atrial Fibrillation in the UK

Saturday, August 27, 2022

1:30 PM – 1:45 PM CEST

Location: C1M1

Publication Number: 177

Background: Direct oral anticoagulants (DOACs) reduce the risk of stroke in patients with nonvalvular atrial fibrillation (AF) but there is an absence of head-to-head comparative studies to inform decision-making using UK real-world data (RWD). Health technology assessment (HTA) agencies such as the National Institute for Health and Care Excellence (NICE) have therefore relied on indirect comparisons with warfarin, which have been limited by trial heterogeneity.

Objectives: To estimate the incidence of stroke and safety outcomes among patients with nonvalvular AF initiating apixaban compared to rivaroxaban using RWD.

Methods: Using anonymized patient data from The Health Improvement Network (THIN®) UK primary care database, we identified adults (≥18 years) with nonvalvular AF newly initiating apixaban or rivaroxaban between 7/2014-12/2020. Patients were required to be naive to study outcomes and other risk factors. Our primary outcome was stroke (ischemic or hemorrhagic), and safety outcomes included all-cause mortality, myocardial infarction (MI), transient ischemic attack (TIA), major bleeding events (MBE), and a composite endpoint of angina/MI/stroke (AMS). We used 1:1 propensity score (PS) matching to balance treatment groups, and high-dimensional PS (hdPS) matching in sensitivity analyses of all outcomes. Patients were followed from the day after treatment initiation until outcome, death, end of patient registration, or end of study period. We estimated hazard ratios (HR) using Cox regression and conducted subgroup analyses by age, concomitant aspirin and prior warfarin use, diabetes, heart failure, and CHA2DS2-VASc score.

Results: We identified 1,839 PS-matched pairs of patients initiating apixaban or rivaroxaban. Compared with rivaroxaban, patients initiating apixaban showed similar rates of stroke (HR, 95% CI: 0.93, 0.64-1.34), all-cause mortality (1.03, 0.87-1.22), MI (0.95, 0.54-1.68), TIA (1.03, 0.61-1.72), and AMS (0.96, 0.72-1.27), and lower rates of MBE (0.60, 0.47-0.75). In subgroup analyses, effects on stroke were heterogeneous by history of warfarin use (with: 0.69, 0.24-1.98; without: 1.19, 0.77-1.85), noting limited power. hdPS-matched results were similar across outcomes.

Conclusions: Among patients with nonvalvular AF, apixaban was as effective as rivaroxaban in reducing rate of stroke and safer in terms of MBE. RWD shows potential to fill evidence gaps and reduce uncertainty in HTA decision making.

Presenting Author(s)

Liza R. Gibbs, MS

Aetion, Inc
Cambridge, Massachusetts, United States

Slides

Co-Author(s)

PG

Priya Govil

Aetion, Inc, United States
SK

Seamus Kent

National Institute for Health and Care Excellence, United Kingdom
SD

Stephen Duffield

National Institute for Health and Care Excellence, United Kingdom
SR

Shaun Rowark

Scientific Adviser
National Institute for Health and Care Excellence, United Kingdom
MS

Manuj Sharma

National Institute for Health and Care Excellence, United Kingdom
AA

Ayad Ali, RPh, MSPharm, PhD, FACE

Senior Director
Aetion, Inc
New York, New York, United States
Amanda Patrick, MS

MS
Aetion, Inc
Concord, Massachusetts, United States
AJ

Ashley Jaksa

Aetion, Inc, United States
PJ

Pall Jonsson

National Institute for Health and Care Excellence, United Kingdom
Nicolle Gatto, PhD, FISPE

Chief Science Officer
Aetion, Inc., United States