Sex‐influence on the time in therapeutic range (TTR) during oral anticoagulation with coumarin derivatives: Systematic review and meta‐analysis

Aims We sought to investigate the association between sex and oral anticoagulation control employing coumarin derivatives. Methods Electronic sources were MEDLINE, Biblioteca Virtual em Saúde (BVS), The Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Cochrane Central and Web of Science. Inclusion criteria were: observational and experimental studies; age ≥18 years; both sexes; treatment with any coumarin derivative for ≥3 months; any indication of long‐term use; quality of oral anticoagulation measured by time in therapeutic range (TTR). The meta‐analysis was developed with odds ratios (OR) for binary variables and mean differences (MD) for continuous variables, using random‐effects models (DerSimonian and Laird) with 95% confidence intervals (CI). Results Overall, 22 articles were selected, comprising 16 cohort studies, four cross‐sectional studies and two clinical trials. The number of participants ranged from 110 to 104 505 (183 612; women: 45%). The main indication of oral anticoagulation was atrial fibrillation. Most studies reported the use of warfarin. In the meta‐analysis, 15 studies were analysed using TTR as a binary variable (OR = 0.87; 95% CI = 0.78, 0.96; z = −2.75; P = .006.; I 2 = 67%) and seven studies as a continuous variable (MD = −2.97; 95% CI = −4.80, −1.14; z = −3.19; P = .0014; I 2 = 75%). The pooled estimates indicated that women were associated with lower TTR than men. Conclusions Our findings revealed an association between female sex and worse oral anticoagulation control. Further studies are needed with primary design to investigate sex‐related factors influencing oral anticoagulation control with coumarin derivatives. Innovative strategies focused on women's health may be useful to improve patient‐centred care.