CO-027Prevalence and bleeding risk associated with the concomitant use of direct oral anticoagulants and antiarrhythmic drugs in patients with atrial fibrillation, based on the french healthcare insurance database

6- Pharmaco-épidémiologie, Pharmacologie sociale et Pharmaco-économie

Thématique principale

1- Cardiovasculaire, respiratoire, rénale, métabolique

L Gosselin ^a, AM Vilcu ^a, C Souty ^a, O Steichen ^b, T Launay ^a, C Conte ^c, B Saint-Salvi ^d, C Turbelin ^a, M Sarazin ^a, T Blanchon ^a, T Hanslik ^e, M Lapeyre-Mestre ^c, L Rossignol ^f. ^aInstitut Pierre Louis D'épidémiologie Et De Santé Publique (iplesp), Sorbonne Université, Inserm - Paris (France); ^bInstitut Pierre Louis D'épidémiologie Et De Santé Publique (iplesp), Sorbonne Université, Inserm, Aphp, Hopital Tenon, Service De Médecine Interne - Paris (France); ^cService De Pharmacologie Médicale Et Clinique, Cic 1436, Chu Toulouse, Inserm, Université De Toulouse (leasp Umr 1027) - Toulouse (France); ^dAgence National De Sécurité Du Médicaments Et Des Produits De Santé - Saint-Denis (France); ^eInstitut Pierre Louis D'épidémiologie Et De Santé Publique (iplesp), Sorbonne Université, Inserm, Aphp, Hopital Ambroise Paré, Service De Médecine Interne - Paris (France); ^fDépartement De Médecine Générale, Université De Paris - Paris (France)

Introduction:Concomitant exposure to direct oral anticoagulants (DOAC) and antiarrhythmic drugs is common in patients with atrial fibrillation (AF). Some antiarrhythmic drugs (amiodarone, verapamil and diltiazem) have moderate CYP3A4-related pharmacokinetic interactions with two DOAC, apixaban and rivaroxaban. We aimed to estimate the prevalence of exposure to this drug-drug association (DDA) and to assess the bleeding risk associated in patients with AF.

Material and methods:We conducted a cohort study using a representative 1/97th sample of the French healthcare insurance database between 2014 and 2018. Patients with AF aged 18 and over were included when apixaban or rivaroxaban was first dispensed and followed-up until hospitalization for bleeding, death, discontinuation of apixaban or rivaroxaban, exposure to a strong CYP3A4 inhibitor, or until December 31st 2018, whichever came first. Primary outcome was hospitalization for bleeding. Patients were considered as exposed to the DDA if they simultaneously received rivaroxaban or apixaban with verapamil, diltiazem, or amiodarone. The association between the exposure to the DDA and hospitalization for bleeding was evaluated as a time-dependent variable in Cox model.

Results:Between 2014 and 2018, the AF population under apixaban or rivaroxaban represented 8,278 patients in the database and the annual average prevalence of DDA exposure in this population was 43.5%. Among the 8,278 patients, 281 (3.4%) were hospitalized for bleeding, of which 102 (36.3%) received the DDA and 179 (63.7%) received apixaban or rivaroxaban alone. There was no association between DDA exposure and risk of hospitalization for bleeding (adjusted HR= 1.14, [0.89, 1.46]). Age (HR 1.03 [1.02, 1.04]), male gender (HR 1.68 [1.30, 2.17]) and diabetes at inclusion (HR 1.37 [1.04, 1.81]) were associated with an increased risk of hospitalization for bleeding.

Discussion / Conclusion:Exposure to antiarrhythmic drugs was not associated with an increased risk of hospitalization for bleeding in patients with AF under rivaroxaban or apixaban; hence, no dosage adjustment seems necessary.

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Keywords:pharmacovigilance, drug interactions, adverse drug reactions, anticoagulants, anti-arrhythmia agents