Investigating sex differences in frailty and its impact on anticoagulation and hospitalization in older patients with atrial fibrillation

Abstract Background Frailty is common in older patients, and it has been suggested to occur more frequently and with greater severity in women compared to men. In older people with atrial fibrillation (AF), frailty has been shown to influence the prescriptions of oral anticoagulants (OAC) and patient outcomes. Purpose To examine the prevalence of frailty in older patients with AF and the association between frailty with OAC prescription and hospitalization, with a particular focus on the impact of sex. Methods Adults aged ≥60 years with AF were recruited at the outpatient clinics of two major hospitals in Vietnam between December 2022 and May 2024. Frailty was defined by the 9-item Clinical Frailty Scale (CFS). Logistic regression models were applied to examine the association between CFS score with OAC prescription and cardiovascular disease (CVD) related hospitalization over 6 months. Results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). An interaction term was added to the models to obtain the women-to-men ratios of ORs and 95% CIs, which were used to evaluate whether the ORs differed between the sexes. Results A total of 1210 patients (513 women, 697 men) were included in this analysis. They had a mean age of 73.7 (SD 8.9) years. The mean CFS score was 4.1 (SD 1.2). Using a cut-point of CFS >=5, the prevalence of frailty was 40.7% in all participants, 46.8% in women vs. 36.3% in men, p<0.001. Women were older (mean age 74.6/ SD 8.9 vs 73.0/ SD 8.8 in men, p=0.004), had higher CHA2DS2-VASc score (4.2/ SD 1.3 vs 3.2/ SD 1.3 in men, p<0.001) and HASBLED score (1.6/ SD 0.8 vs 1.4/ SD 0.8, p=0.004). OAC prescription rate was 90.7% in all participants and lowest among frail women (83.8%) (Figure 1). With every unit increase in the CFS score, the adjusted ORs for OAC prescription were 0.70 (95%CI 0.54 – 0.90) in women, 0.97 (95%CI 0.74 – 1.28) in men (women-to-men ratio of ORs 0.72, 95%CI 0.50 - 1.05). During the 6-month follow-up, the CVD hospitalization rate was 14.3%. CFS score predicted CVD hospitalization, with the adjusted ORs of 1.65 (95%CI 1.29 – 2.10) in women, 2.04 (95%CI 1.62 – 2.59) in men, women-to-men ratio of ORs 0.81 (95%CI 0.58 – 1.13). (Figure 2) Conclusion In older patients with AF, women had a higher burden of frailty, and increased risks of stroke and bleeding. Frailty was associated with a reduced likelihood of receiving OAC in women. Frailty increased the risk of CVD hospitalization for both women and men, although its impact on hospitalization tends to be greater in men. These findings align with the observed sex-frailty paradox in older adults in general. Further studies are needed to confirm these findings.Figure 1 Figure 2