loading page

Outcomes of real-world patients with non-valvular atrial fibrillation on anticoagulants ineligible for Phase III trials of direct oral anticoagulants
  • +1
  • Mayumi Higa,
  • Takeshi Morinoto,
  • Masayuki Ikeda,
  • Shinichiro Ueda
Mayumi Higa
University of the Ryukyus Faculty of Medicine Graduate School of Medicine
Author Profile
Takeshi Morinoto
Hyogo College of Medicine
Author Profile
Masayuki Ikeda
Kagawa University Faculty of Medicine Graduate School of Medicine
Author Profile
Shinichiro Ueda
University of the Ryukyus

Corresponding Author:[email protected]

Author Profile

Abstract

Aims: 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 eligibility of patients 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. Nearly half (48.2%, n=3772) of these patients were ineligible for phase III trials of direct oral anticoagulants, mainly because of low CHADS2 scores (26.4%), renal dysfunction (9.5%), anemia (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. Conclusions: 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 the real-world safety and efficacy of anticoagulants.
22 Aug 2023Submitted to British Journal of Clinical Pharmacology
22 Aug 2023Submission Checks Completed
22 Aug 2023Assigned to Editor
22 Aug 2023Review(s) Completed, Editorial Evaluation Pending
24 Aug 2023Reviewer(s) Assigned