Alice Ballerie1, Rémi Nguyen Van2, Karine Lacut3, Hubert Galinat4, Chloé Rousseau5, Adeline Pontis6, Fabienne Nédelec-Gac6, Alain Lescoat1, Nicolas Belhomme2, Pierre Guéret6, Guillaume Mahé7, Francis Couturaud3, Patrick Jégo1, Isabelle Gouin-Thibault8. 1. Department of Internal Medicine and Clinical Immunology, Rennes University Hospital, Rennes, France; Univ Rennes, Rennes University Hospital, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Rennes, France. 2. Department of Internal Medicine and Clinical Immunology, Rennes University Hospital, Rennes, France. 3. Department of Internal Medecine and Chest Diseases, Brest University Hospital, Bretagne Occidentale University, EA 3878, CIC INSERM 1412, Brest, FCRIN INNOVTE, France. 4. Hematology Laboratory, Brest University Hospital, Bretagne Occidentale University, EA 3878, Brest, France. 5. Clinical Investigation Center INSERM 1414, Department of Clinical Pharmacology, Rennes University Hospital, F-35033, France. 6. Hematology Laboratory, Rennes University Hospital, Rennes, France. 7. Vascular Medicine Unit, Rennes University Hospital, INSERM CIC 1414, Clinical Investigation Center, Univ Rennes, M2S - EA 7470, F-35033 Rennes, France. 8. Univ Rennes, Rennes University Hospital, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Rennes, France; Hematology Laboratory, Rennes University Hospital, Rennes, France. Electronic address: isabelle.gouin@chu-rennes.fr.
Abstract
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.
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.