PT - JOURNAL ARTICLE AU - Chobanov, Jan D AU - Wang, Zixuan AU - Man, Kenneth K C AU - Dayib, Edil AU - Lip, Gregory Y H AU - Hingorani, Aroon D AU - Leung, Wai K AU - Wong, Ian C K AU - Mongkhon, Pajaree AU - Lau, Wallis C Y TI - Sex-specific comparative outcomes between oral anticoagulants in patients with atrial fibrillation: a systematic review and meta-analysis AID - 10.1136/openhrt-2024-002792 DP - 2024 Jul 01 TA - Open Heart PG - e002792 VI - 11 IP - 2 4099 - http://openheart.bmj.com/content/11/2/e002792.short 4100 - http://openheart.bmj.com/content/11/2/e002792.full SO - Open Heart2024 Jul 01; 11 AB - Aims Women with atrial fibrillation (AF) are under-represented in randomised controlled trials (RCTs) of direct oral anticoagulants (DOACs). This systematic review and meta-analysis of RCTs and observational studies examined sex-specific outcomes of DOACs in AF.Methods PubMed, Embase, Web of Science and Cochrane Library were searched from January 2008 to November 2022. Sex-specific comparative outcomes of stroke/systemic embolism (SE), major bleeding, intracranial haemorrhage (ICH) and gastrointestinal bleeding (GIB) between oral anticoagulants were pooled using random effects models. P values for interaction were calculated to examine differences in results between sexes. RCTs and observational studies were meta-analysed separately.Results 5 RCTs and 33 observational studies were included, totalling 1 085 931 women and 1 387 123 men. Meta-analyses showed that for both sexes, DOAC versus warfarin was generally associated with lower risk of stroke/SE, major bleeding and ICH; in DOAC–DOAC comparisons, rivaroxaban versus dabigatran had higher GIB risk. The only sex-specific difference observed was that when compared with warfarin, women had higher GIB risk with rivaroxaban (women: pooled risk ratio (pRR)=1.34, 95% CI=1.18 to 1.51; men: pRR=0.97, 95% CI=0.85 to 1.10; p value for interaction (p for interaction)<0.001) and possibly dabigatran (women: pRR=1.25, 95% CI=0.92 to 1.70; men: pRR=0.83, 95% CI=0.72 to 0.97; p-for-interaction=0.02). The sex difference in GIB remained for rivaroxaban when a Bonferroni-corrected significance level was used (α=0.003). No sex-specific GIB data for apixaban and edoxaban was available for the meta-analysis.Conclusions For both sexes, DOACs generally demonstrated favourable effectiveness and safety over warfarin. However, observational data suggested that women may have higher GIB risk with rivaroxaban and possibly dabigatran than warfarin. Further studies are warranted to verify our findings and elucidate sex-specific GIB risk with apixaban and edoxaban, of which the data is currently lacking.PROSPERO registration number CRD42022325027.All data relevant to the study are included in the article or uploaded as online supplemental information.