Use of apixaban in adults with congenital heart disease and atrial arrhythmias: The PROTECT-AR study

Αναστάσιος Κάρτας; Αndreas S. Papazoglou; Dimitrios V. Moysidis; Stefanos Despotopoulos; Amalia Baroutidou; Diamantis Kosmidis; Athanasios Koutsakis; Sotiria Liori; Sotiria Apostolopoulou; Alexandra Frogoudaki; Afrodite Tzifa; Απόστολος Γαλατάς; G Alexandridis; Efstathios Spiridonidis; Ioannis Doundoulakis; Efstratios Karagiannidis; Haralambos Karvounis; Antonios Ziakas; George Giannakoulas

doi:10.1016/j.ijcard.2024.131993

Graphical abstract published by International Journal of Cardiology — Graphical abstract · Published by International Journal of Cardiology · CC BY 4.0

Why the study?

Adults with congenital heart disease and atrial arrhythmias have an increased thromboembolic risk, but limited data exist on non-vitamin K oral anticoagulants in this population.

Does apixaban prevent stroke or thromboembolism in adults with congenital heart disease and atrial arrhythmias compared to historical vitamin K antagonist use?

Structured PICO

Does apixaban prevent stroke or thromboembolism in adults with congenital heart disease and atrial arrhythmias compared to historical vitamin K antagonist use?

P

Population

218 adults with congenital heart disease (ACHD) and atrial arrhythmias (atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia)

I

Intervention

Routine apixaban treatment

C

Comparator

Historical control of vitamin K antagonist (VKA) use (analyzed prior to transition to apixaban)

O

Outcome

Composite of stroke or thromboembolismcomposite

In adults with congenital heart disease and atrial arrhythmias, routine apixaban use is non-inferior to historical vitamin K antagonist use for preventing stroke or thromboembolism, with comparable major bleeding risk.

Implication

Apixaban may be feasible for thromboprophylaxis in ACHD with AA; leaves open need for RCTs to guide practice.

Abstract

Background Adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) face an increased risk of thromboembolic events. Limited data exist on the use of non-vitamin K oral anticoagulants for thromboprophylaxis in ACHD. We aimed to assess the effectiveness and safety of apixaban in ACHD patients with AA. Methods PROTECT-AR (NCT03854149) was a prospective, multicenter, observational study conducted from 2019 to 2023. ACHD patients with atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia on routine apixaban treatment were included. The historical control group consisted of patients previously on vitamin K antagonist (VKA), who were analyzed prior to their transition to apixaban. The primary effectiveness endpoint was the composite of stroke or thromboembolism. The primary safety endpoint was major bleeding. Results The study enrolled 218 ACHD patients with AA on apixaban, of which 73 were previous VKA users. The analysis covered 527 patient-years of prospective exposure to apixaban and 169 patient-years of retrospective exposure to VKA. The annualized rate of stroke or thromboembolism was 0.6% in the apixaban group and 1.8% in the VKA group (absolute difference − 1.2%; upper limit of one-sided 95% confidence interval [CI] 0.9%, lower than the predefined non-inferiority margin of +1.8%, P non-inferiority < 0.001). The annualized rate of major bleeding was 1.5% in the apixaban group and 2.4% in the VKA group (hazard ratio 0.64; 95% CI 0.19–2.10, P = 0.48). Conclusion In ACHD patients with AA, routine apixaban use exhibited a non-inferior rate of stroke or thromboembolism compared to historical VKA use, alongside a similar rate of major bleeding.