In AF patients, frailty doubled the risk of major bleeding, and experiencing major bleeding showed a trend toward a higher risk of death or MACE (HR 5.02; 95% CI 0.87-28.97).
Observational (n=12,360)
Yes
Does the presence of clinical complexity features increase the risk of major bleeding and subsequent adverse outcomes in patients with atrial fibrillation?
In patients with atrial fibrillation, frailty significantly increases the risk of major bleeding, which in turn trends toward a higher risk of subsequent death and MACE.
Effect estimate: HR 5.02 (95% CI 0.87-28.97)
Abstract Background Clinical complexity features, such as multimorbidity, polypharmacy and frailty, emerged as significant determinants of clinical course in patients with atrial fibrillation (AF). Evidence suggests that clinical complexity affects major bleeding (MB) risk. Purpose We aimed to investigate the impact of clinical complexity features on the risk of MB events and the subsequent impact on adverse outcomes using a multistate model analysis. Methods We analysed AF patients from two large prospective observational registries, one conducted in Europe and one in Asia. Using multistate models, we examined transitions from baseline to MB events and, ultimately, to a composite outcome of all-cause death and major adverse cardiovascular events (MACEs). We examined the effects of multimorbidity, frailty and polypharmacy on transition rates using Cox proportional hazards regression models. We then evaluated the impact of the transition to MB events on the risk of adverse outcomes, adjusted according to the presence of the clinical complexity features. Results 12,360 patients with AF (mean age 68.9, SD 11.6 years; 38.7% female) were included in the analysis. Over a median follow-up of 696 days (IQR 365–735), 204 patients (1.6%, incident rate IR 1.1 per 100 person-years pys) had MB events, of whom 36 (17.6%, IR 17.4 per 100 pys) later experienced the composite outcome. An additional 1,151 patients (9.3%, IR 5.9 per 100 pys) transitioned directly from baseline to the composite outcome. Prevalence of multimorbidity (p0.001), polypharmacy (p0.001) and frailty (p=0.004) were higher in those patients experiencing MB. After adjustments, being pre-frail or frail was associated with a 2-fold higher risk of experiencing a MB event Figure 1. In contrast, all three clinical complexity features were independently associated with transitioning directly to a composite outcome event Figure 1. After adjusting for the presence of multimorbidity, polypharmacy and frailty, patients who experienced MB showed a trend in higher risk of the composite outcome than those who did not (HR 5.02, 95% CI 0.87–28.97, Figure 2). Conclusions In AF patients, the presence of frailty significantly increased the risk of MB. After adjusting for clinical complexity features, patients reporting a MB event showed a trend in higher risk for the composite outcome, compared to those who did not. Integrated care strategies are needed to control for the risk of MB and subsequent adverse outcomes.Clinical Complexity and Transitions Cumulative Transition Rates
Proietti et al. (2025) conducted an observational in Atrial Fibrillation (n=12,360). Major bleeding event vs. No major bleeding event was evaluated on Composite outcome of all-cause death and major adverse cardiovascular events (MACEs) (HR 5.02, 95% CI 0.87-28.97). In AF patients, frailty doubled the risk of major bleeding, and experiencing major bleeding showed a trend toward a higher risk of death or MACE (HR 5.02; 95% CI 0.87-28.97).