Study type

Study type

Non-interventional study

Scope of the study

Effectiveness study (incl. comparative)
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Anatomical Therapeutic Chemical (ATC) code

(B01AF02) apixaban
apixaban
(B01AF01) rivaroxaban
rivaroxaban
(B01AF03) edoxaban
edoxaban
(B01AE07) dabigatran etexilate
dabigatran etexilate

Medical condition to be studied

Atrial fibrillation
Population studied

Age groups

Adults (18 to < 46 years)
Adults (46 to < 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Estimated number of subjects

13991
Study design details

Main study objective

This study aims to evaluate the incidence of stroke and other outcomes in association with direct oral anticoagulants (DOACs) as compared to each other (i.e. direct comparisons) among patients with nonvalvular atrial fibrillation (AFib) in the UK. Individual DOACs of interest include apixaban, rivaroxaban, edoxaban, and dabigatran.

Outcomes

The primary objective is to: Estimate the incidence rates and evaluate the association of stroke (ischemic or hemorrhagic) for patients with nonvalvular AFib who initiated apixaban compared to rivaroxaban, The secondary objectives are to: Compare the incidence rates of stroke for patients who initiated: apixaban compared to edoxaban, dabigatran, and DOACs class, rivaroxaban compared to edoxaban, dabigatran, and DOACs class, edoxaban compared to DOACs class, dabigatran compared to DOACs class, Compare the incidence rates of secondary outcomes for the each head to head comparison.

Data analysis plan

In each comparison cohort, propensity score matching between exposure groups will be performed using 1:1 nearest neighbor matching without replacement with a maximum matching caliper of 0.01. In addition to graphical depictions of propensity score distributions, the absolute standardized differences (ASD) in proportions and means of baseline characteristics will be estimated to examine comparability of exposure groups. Cox proportional hazards regression (outcomes model) will be used to estimate hazard ratios and 95% CI for each outcome after propensity score matching. The incidence of stroke and secondary outcomes will be compared between individual DOACs in primary and secondary comparisons as mutually exclusive cohorts. High-dimensional propensity score (HdPS) analysis will be used as a sensitivity analysis to estimate the association between treatment with DOACs and the primary outcome of stroke.
Documents
Study publications
Jaksa A, Gibbs L, Kent S, Rowark S, Duffield S, Sharma M, Kincaid L, Ali AK, Pa…