title: Balancing thromboembolic and bleeding risk with non-vitamin K antagonist oral anticoagulants (NOACs): A systematic review and meta-analysis on gender differences.
abstract: Sex and gender differences have been reported in atrial fibrillation (AF), especially in relation to differences in thromboembolic and bleeding risks. More recently, pharmacological treatments have changed following the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) progressively replacing vitamin K antagonists (VKAs). The aims of this systematic review are to summarize the available evidence on NOACs and the relationship to major adverse outcomes according to sex. Moreover, we performed a meta-analysis of data from the phase III clinical trials investigating the sex effect on stroke/systemic embolic events (SEE) and major bleeding. Our literature review found small differences in NOACs efficacy and safety between male and female patients, even if so far available literature is limited to post-hoc ancillary analyses from randomized trials and one cohort study. Meta-analysis from NOAC trials found a differential effect of NOACs, with male patients being more protected from stroke/SEE and female patients more protected from major bleeding events. Further data are needed to fully elucidate sex differences in AF patients treated with NOACs.
authors.affiliation: University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom. Electronic address: marco.proietti@uniroma1.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Proietti
authors.affiliation: University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom.
authors.forename: Paola
authors.initials: P
authors.lastname: Cheli
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza-University of Rome, Rome, Italy; Research Center on Gender and Evaluation and Promotion of Quality in Medicine (CEQUAM), Sapienza-University of Rome, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Basili
authors.affiliation: University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom; Department of Cardiology, Congenital Heart Diseases and Electrotherapy, Silesian Medical University, Silesian Centre for Heart Diseases, Zabrze, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Mazurek
authors.affiliation: University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000009:adverse effects*; D017326:Clinical Trials, Phase III as Topic; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D012306:Risk; D012727:Sex Characteristics; D013923:Thromboembolism / Q000139:chemically induced*
chemical_list: D000925:Anticoagulants
keywords: Atrial fibrillation; Gender; Major bleeding; Non-vitamin K antagonist oral anticoagulants; Stroke