Abstract 15734: Assessment of Generalizability in Phase 3 Clinical Trials of Direct Oral Anticoagulants by Eligibility to Trials and Outcomes of Real World Patients With Non-Valvular Atrial Fibrillation

• Published in: Circulation (New York, N.Y.) Vol. 140; no. Suppl_1 Suppl 1; p. A15734
• Main Authors: HIga, Mayumi, Une, Kaori, Ueda, Shinichiro
• Format: Journal Article
• Language: English
• Published: by the American College of Cardiology Foundation and the American Heart Association, Inc 19-11-2019
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.140.suppl_1.15734

Study ObjectivesPhase III trials of direct oral anticoagulants (DOACs) showed non-inferiority in terms of efficacy and safety to warfarin and have been increasingly prescribed in patients with non-valvular atrial fibrillation(NVAF). Success in DOAC trials for the regulatory approval does not guarantee safety and effectiveness in real world clinical practice since external validity of results has not fully estimated. In this study, we assessed generalizability of phase III trials of DOACs.MethodsWe conducted a retrospective cohort study which consecutively registered and followed for 4 years 2980 patients who were newly diagnosed as NVAF after 13th of March 2011 and started receiving DOACs or warfarin. This time point was set because the first DOAC was launched in Japan. The primary outcome was major bleeding according to ISTH and TIMI criteria and secondary outcomes were stroke and systemic embolism, mortality and myocardial infarction. We matched characteristics of our patients against inclusion and exclusion criteria of each phase III trials and compared incidence rates of outcome in our cohort to those in phase III trials.ResultsApproximately half (RELY, ROCKET-AF, ENGAGE) and 70% (ARISTOTLE ) of our patients were eligible to phase III trials. The incidence rate of major bleeding in our cohort was similar to that in Phase 3 trials other than ENGAGE (Table). Risk reduction in major bleeding by DOAC was consistently observed in our cohort and phase 3 trials other than ROCKET AF. Fewer stroke and systemic embolism also were also consistently showed in phase 3 trials and our cohort.ConclusionsApproximately 50 to 70 % of NVAF patients from real world clinical practice were eligible to the phase 3 trials of DOACs. Given that relatively high eligibility and outcome profiles which do not differ so much between the cohort and clinical trials, results from phase 3 trials can be applied to patients in real world clinical practice.