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