Efficacy and safety of direct oral anticoagulants versus vitamin K antagonists in patients on chronic dialysis
Authors: Laville Solène M , Couchoud Cécile , Bauwens Marc , Vacher-Coponat Henri , Choukroun Gabriel , Liabeuf Sophie ,   for the REIN Collaborators, Honoré Nadia , Boime Sabrina , Gardeur-Algros Emilie , Chantrel François , Larre Xabina , Leffoné Karen , Reydit Mathilde , Cellarier Eric , Girault Patricia , Tiple Aurélien , Caillet Aurélie , Ceruasuolo Damiano , Béchade Clémence , Roche Sophie , Tenon-Franzin Anaïs , Bemrah Abdelkader , Siebert Muriel , Bayat Sahar , Vigneau Cécile , Naudin Marine , Halimi Jean-Michel , Sautenet Bénédicte , Varnier Anne-Lise , Arnoult Gwendoline , Wolak Aurore , Kazès Isabelle , Izaaryene Ghizlane , Mazoué Franck , Cremades Adeline , Gentile Stéphanie , Brunet Philippe , Savet Caroline , Desmaret Maxime , Courivaud Cécile , Janetta Cécilia Citadelle , Deloumeaux Jacqueline , Galantine Valérie , Rochemont Devi , Sow Mamadou Khali , Nacher Mathieu , Wurtz Blandine , Marini Hélène , Edet Stéphane , Ducamp Evelyne , Cherquaoui Zoubair , Baouche Hayet , Tebbakh Houssem Eddine , Jais Jean-Philippe , Mercadal Lucile , Hôpitalde la Pitié , Belkacemi Mohamed , Duny Yohan , Martin Mélanie , Daurès Jean-Pierre , Moranne Olivier , Glaudet Florence , Vergnenègre Alain , Touré Fatouma , Monzel Marie-Rita , Vogel Véronique , Erpelding Marie-Line , Melchior Philippe , Ziegler Amandine , Laurain Emmanuelle , Bideau Aurélie , Merle Sylvie , Ranlin Alex , Schmitt Violaine , Marimoutou Catherine , Coponat Henri Vacher , Lapalu Sophie , Brun Ludivine , Lepage Benoît , Longlune Nathalie , Gomis Sébastien , Foulon Carole , Hazzan Marc , Glowacki François , Baroux Noemie , Tivollier Jean-Michel , Hami Assia , Lemauft Jean Xavier , Nguyen Jean-Michel , Lavainne Frédéric , Hogan Julien , Joly Amélie , Sarraj Ayman , Duthe Fabien , Ayrault Bénédicte , Bauwens Marc , Pierron Marie Hélène , Testevuide Pascale , Boyer Sylvie , Mérono Agnès , Guillermin Marie-Noëlle , Galland Roula , Babinet François 
Published: February 2024

ABSTRACT

Background
Clinical trials of direct oral anticoagulants (DOAC) are scarce and inconclusive in patients who are receiving dialysis, for whom DOAC are not labelled in Europe. In a French nationwide registry study of patients on chronic dialysis, we compared the effectiveness and safety of off-label DOAC use vs approved vitamin K antagonist (VKA).

Methods
Data on patients on dialysis were extracted from the French Renal Epidemiology and Information Network (REIN) registry and merged with data from the French national healthcare system database (Système National des Données de Santé, SNDS). Patients on dialysis who had initiated treatment with an oral anticoagulant between 1 January 2012 and 31 December 2020, were eligible for inclusion. The primary safety outcome was the occurrence of major bleeding events and the primary effectiveness outcome was the occurrence of thrombotic events. Using propensity score–weighted cause-specific Cox regression, we compared the safety and effectiveness outcomes for DOAC and VKA.

Results
A total of 8954 patients received an oral anticoagulant (483 DOAC and 8471 VKA) for the first time after the initiation of dialysis. Over a median (interquartile range) follow-up period of 1.7 (0.8–3.2) years, 2567 patients presented a first thromboembolic event and 1254 patients had a bleeding event. After propensity score adjustment, the risk of a thromboembolic event was significantly lower in patients treated with a DOAC than in patients treated with a VKA {weighted hazard ratio (wHR) [95% confidence interval (CI)] 0.66 (0.46; 0.94)}. A non-significant trend toward a lower risk of major bleeding events was found in DOAC-treated patients, relative to VKA-treated patients [wHR (95% CI) 0.68 (0.41; 1.12)]. The results were consistent across subgroups and in sensitivity analyses.

Conclusions
In a large group of dialysis patients initiating an oral anticoagulant, the off-label use of DOACs was associated with a significantly lower risk of thromboembolic events and a non-significantly lower risk of bleeding, relative to VKA use. This provides reassurance regarding the off-label use of DOACs in people on dialysis.