Eligibility
Our inclusion and exclusion criteria, which were derived from the most
commonly used criteria of four DOACs Phase III trials, were considered
valid for assessing eligibility and comparing outcomes between eligible
and ineligible patients because the proportion of eligible patients
using our criteria did not differ significantly from those using the
criteria of the individual Phase III trials (Table S1 ).
Notably, several studies have reported the proportion of “real-world”
patients with NVAF eligible for Phase III trials. In a UK general
practice database study,8 68% of patients would be
eligible for RE-LY, compared with 65% and 51% for ARISTOTLE and
ROCKET-AF, respectively. A retrospective cross-sectional database
analysis at the University Hospital Stroke Unit in
Belgium11 found that 47.6% of patients were eligible
for RE-LY, 45.5% for ARISTOTLE, and 39.3% for ROCKET-AF. A study of
patients with a discharge diagnosis of AF in a large public hospital
network in Melbourne, Australia, showed that 60.5%, 52.6%, and 35.8%
of patients would have been eligible for the ARISTOTLE, RE-LY, and
ROCKET-AF trials, respectively.12 Of the patients with
NVAF in the MAQI2 registry in Michigan, USA, 54.5% would meet the
selection criteria used in RE-LY, 39.1% for ROCKET-AF, and 59.9% for
ARISTOTLE.13 The reported proportions of patients
eligible for Phase III trials of DOACs in real-world practice, including
our results, were consistently around 50%, although there were some
differences among studies.
The ineligible patients were mainly characterised by low
CHADS2 scores, renal dysfunction, anaemia, and chronic
NSAID use. The latter three are well-known risk factors for major
bleeding in patients with NVAF treated with anticoagulation. However,
elderly patients with these risk factors are often encountered in
real-world clinical practice, and anticoagulation should be considered
in the presence of atrial fibrillation. The studies cited above also
reported a high risk of bleeding, poor renal function, and concomitant
use of aspirin and antiplatelet agents as reasons for not enrolling in
the Phase III trial, despite taking anticoagulants in actual
practice.12,13