ABSTRACT
Aim: To compare the outcomes of real-world Japanese patients
with nonvalvular atrial fibrillation who are ineligible for Phase III
trials of direct oral anticoagulants with those of eligible patients.
Methods: In retrospective cohort design, consecutively
registered patients with nonvalvular atrial fibrillation who had taken
warfarin were followed up and assessed patients’ eligibility for Phase
III trials of direct oral anticoagulants. The effects of the
ineligibility of patients on outcomes were estimated using Cox
proportional hazards models to calculate the hazard ratio (HR) and 95%
confidence interval.
Results: We registered 7826 Japanese patients with nonvalvular
atrial fibrillation from 71 hospitals. Approximately half (48.2%,
n=3772) of these patients were ineligible for Phase III trials of direct
oral anticoagulants, mainly because of low
CHADS2scores (26.4%), renal dysfunction (9.5%), anaemia (6.4%), and chronic
treatment with nonsteroidal anti-inflammatories (4.0%). After excluding
patients with a CHADS2 score <2 (n=2064,
26.4%) from total ineligible patients, the remaining ineligible
patients (n=1708) exhibited significantly greater risks of major
bleeding (unadjusted hazard ratio 2.00, 95% confidence interval
1.63–2.44, p <0.0001), stroke/systemic embolism
(unadjusted hazard ratio 1.53, 95% confidence interval 1.17–1.98,p =0.0016), and all-cause mortality (unadjusted hazard ratio 2.84,
95% confidence interval 2.36–3.43, p <0.0001) compared
to the eligible patients.
Conclusion: The benefits and risks of direct oral
anticoagulants suggested by Phase III trials may not necessarily apply
to patients ineligible for Phase III trials. This gap between evidence
and practice is an issue in anticoagulants’ real-world safety and
efficacy.