TY - JOUR
T1 - Major bleeding in users of direct oral anticoagulants in atrial fibrillation: A pooled analysis of results from multiple population-based cohort studies
AU - van den Ham, Hendrika A.
AU - Souverein, Patrick C.
AU - Klungel, Olaf H.
AU - Platt, Robert W.
AU - Ernst, Pierre
AU - Dell'Aniello, Sophie
AU - Schmiedl, Sven
AU - Grave, Birgit
AU - Rottenkolber, Marietta
AU - Huerta, Consuelo
AU - Martin Merino, Elisa
AU - Leon-Munoz, Luz M.
AU - Montero, Dolores
AU - Andersen, Morten
AU - Aakjaer, Mia
AU - De Bruin, Marie L.
AU - Gardarsdottir, Helga
PY - 2021
Y1 - 2021
N2 - ObjectiveTo establish the risk of major bleeding in direct oral anticoagulant (DOAC) users (overall and by class) versus vitamin K antagonist (VKA) users, using health care databases from four European countries and six provinces in Canada.MethodsA retrospective cohort study was performed according to a similar protocol. First-users of VKAs or DOACs with a diagnosis of non-valvular atrial fibrillation (NVAF) were included. The main outcome of interest was major bleeding and secondary outcomes included gastrointestinal (GI) bleeding and intracranial haemorrhage (ICH). Incidence rates of events per 1000 person years were calculated. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated using a Cox proportional hazard regression model. Exposure and confounders were measured and analysed in a time-dependant way. Risk estimates were pooled using a random effect model.Results421 523 patients were included. The risk of major bleeding for the group of DOACs compared to VKAs showed a pooled HR of 0.94 (95% CI: 0.87–1.02). Rivaroxaban showed a modestly increased risk (HR 1.11, 95% CI: 1.06–1.16). Apixaban and dabigatran showed a decreased risk of respectively HR 0.76 (95% CI: 0.69–0.84) and HR 0.85 (95% CI: 0.75–0.96).ConclusionsThis study confirms that the risk of major bleeding of DOACs compared to VKAs is not increased when combining all DOACs. However, we observed a modest higher risk of major bleeding for rivaroxaban, whereas for apixaban and dabigatran lower risks of major bleeding were observed compared to VKAs.
AB - ObjectiveTo establish the risk of major bleeding in direct oral anticoagulant (DOAC) users (overall and by class) versus vitamin K antagonist (VKA) users, using health care databases from four European countries and six provinces in Canada.MethodsA retrospective cohort study was performed according to a similar protocol. First-users of VKAs or DOACs with a diagnosis of non-valvular atrial fibrillation (NVAF) were included. The main outcome of interest was major bleeding and secondary outcomes included gastrointestinal (GI) bleeding and intracranial haemorrhage (ICH). Incidence rates of events per 1000 person years were calculated. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated using a Cox proportional hazard regression model. Exposure and confounders were measured and analysed in a time-dependant way. Risk estimates were pooled using a random effect model.Results421 523 patients were included. The risk of major bleeding for the group of DOACs compared to VKAs showed a pooled HR of 0.94 (95% CI: 0.87–1.02). Rivaroxaban showed a modestly increased risk (HR 1.11, 95% CI: 1.06–1.16). Apixaban and dabigatran showed a decreased risk of respectively HR 0.76 (95% CI: 0.69–0.84) and HR 0.85 (95% CI: 0.75–0.96).ConclusionsThis study confirms that the risk of major bleeding of DOACs compared to VKAs is not increased when combining all DOACs. However, we observed a modest higher risk of major bleeding for rivaroxaban, whereas for apixaban and dabigatran lower risks of major bleeding were observed compared to VKAs.
KW - atrial fibrillation
KW - cohort studies
KW - directoral anticoagulants
KW - major bleeding
KW - oral anticoagulants
KW - vitamin K antagonists
U2 - 10.1002/pds.5317
DO - 10.1002/pds.5317
M3 - Journal article
C2 - 34173286
VL - 30
SP - 1339
EP - 1352
JO - Pharmacoepidemiology and Drug Safety
JF - Pharmacoepidemiology and Drug Safety
SN - 1053-8569
IS - 10
ER -