Apixaban and rivaroxaban in obese patients treated for venous thromboembolism: Drug levels and clinical outcomes

Alice Ballerie (1, 2) , Rémi Nguyen Van (3) , Karine Lacut (4, 5) , Hubert Galinat (4) , Chloé Rousseau (3, 6) , Adeline Pontis (3, 6) , Fabienne Nédelec-Gac (3) , Alain Lescoat (1, 2, 3) , Nicolas Belhomme (3) , Pierre Guéret (3) , Guillaume Mahé (7, 6, 3) , Francis Couturaud (4, 5) , Patrick Jégo (1, 2) , Isabelle Gouin-Thibault (3, 6, 1)

1 Irset - Institut de recherche en santé, environnement et travail
2 EHESP - École des Hautes Études en Santé Publique [EHESP]
3 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
4 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
5 CIC Brest
6 CIC - Centre d'Investigation Clinique [Rennes]
7 M2S - Laboratoire Mouvement Sport Santé

BACKGROUND: Direct oral anticoagulants (DOAC) use remains challenging in obese patients treated for Venous-Thrombo-Embolism (VTE) due to the paucity of prospective and dedicated studies. OBJECTIVE: To assess rivaroxaban and apixaban concentrations at different time-points after intake, in obese patients followed at a thrombosis center and treated for VTE; to define factors associated with DOAC levels outside the on-therapy ranges; and to evaluate bleeding and thrombosis rates during follow-up. METHODS: Observational prospective study in two French University hospitals. Apixaban or rivaroxaban concentrations were measured after the first visit, regardless of last intake in obese patients receiving DOAC for VTE. Concentrations were compared to published reference values for non-obese patients. Demographic, clinical, biological and therapeutic data were collected. Univariate and multivariate analyses were performed to identify factors associated to DOAC concentrations outside the on-therapy ranges. RESULTS: Out of the 146 patients included, 22 (15%) had DOAC concentrations outside the on-therapy ranges, mainly in the rivaroxaban group (n = 17). Age ≤ 63 years, use of rivaroxaban and time since last intake ≤8 h were associated with DOAC concentrations outside the on-therapy ranges, in multivariable analysis. During the median follow-up of 16 months, two (1%) patients receiving apixaban had recurrent VTE. No patient had major bleeding, 11 (8%) patients had minor bleeding. CONCLUSION: In this specific prospective bi-centric study dedicated to VTE obese patients, use of DOACs at fixed doses led to concentrations similar to those of non-obese patients in a high proportion of patients, without any effect of the BMI, and with risk-benefit profile comparable to non-obese patients.

Mots clés: Apixaban; Hemorrhage; Obesity; Rivaroxaban; Venous thromboembolism

Domaines: Sciences du Vivant [q-bio]

Alice Ballerie, Rémi Nguyen Van, Karine Lacut, Hubert Galinat, Chloé Rousseau, et al.. Apixaban and rivaroxaban in obese patients treated for venous thromboembolism: Drug levels and clinical outcomes. Thrombosis Research, 2021, 208, pp.39-44. ⟨10.1016/j.thromres.2021.10.009⟩. ⟨hal-03414584⟩