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

Anastasios Kartas; Andreas S Papazoglou; Dimitrios V Moysidis; Stefanos Despotopoulos; Amalia Baroutidou; Diamantis Kosmidis; Athanasios Koutsakis; Sotiria Liori; Sotiria Apostolopoulou; Alexandra Frogoudaki; Afrodite Tzifa; Apostolos Galatas; Georgios Alexandridis; Efstathios Spiridonidis; Ioannis Doundoulakis; Efstratios Karagiannidis; Haralambos Karvounis; Antonios Ziakas; George Giannakoulas

doi:10.1016/j.ijcard.2024.131993

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

Int J Cardiol. 2024 Mar 31:131993. doi: 10.1016/j.ijcard.2024.131993. Online ahead of print.

Authors

Anastasios Kartas¹, Andreas S Papazoglou¹, Dimitrios V Moysidis¹, Stefanos Despotopoulos², Amalia Baroutidou¹, Diamantis Kosmidis¹, Athanasios Koutsakis¹, Sotiria Liori³, Sotiria Apostolopoulou², Alexandra Frogoudaki³, Afrodite Tzifa⁴, Apostolos Galatas¹, Georgios Alexandridis¹, Efstathios Spiridonidis¹, Ioannis Doundoulakis³, Efstratios Karagiannidis¹, Haralambos Karvounis¹, Antonios Ziakas¹, George Giannakoulas⁵

Affiliations

¹ First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636 Thessaloniki, Greece.
² Department of Pediatric and Adult Congenital Heart Disease, Onassis Cardiac Surgery Center, Athens, Greece.
³ Second Department of Cardiology, Attikon University Hospital, Athens, Greece.
⁴ Department of Congenital Heart Disease, Mitera Childrens' Hospital, Athens, Greece.
⁵ First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636 Thessaloniki, Greece. Electronic address: ggiannakoulas@auth.gr.

PMID: 38565389
DOI: 10.1016/j.ijcard.2024.131993

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.

Keywords: Apixaban; Atrial arrhythmias; Bleeding; Congenital heart disease; Stroke.