Higher frailty index scores increased stroke risk by over 5-fold (HR 5.01) for FI 0.3-0.4 and over 6-fold (HR 6.35) for FI ≥0.4 versus FI <0.3 in patients with AF and HFpEF during 36 months follow-up.
RCT (n=721)
Double-blind
Randomized controlled trial (TOPCAT)
Yes
Does a higher degree of frailty increase the risk of stroke and other adverse outcomes in patients with comorbid atrial fibrillation and HFpEF?
In patients with comorbid AF and HFpEF, a higher frailty index is strongly associated with a dose-dependent increase in the risk of stroke, cardiovascular death, and all-cause mortality.
Effect estimate: HR 5.01 for FI 0.3-0.4; HR 6.35 for FI ≥0.4 versus FI <0.3 (95% CI 95% CI 2.00–12.53 for FI 0.3-0.4; 2.26–17.86 for FI ≥0.4)
p-value: p=0.001 for FI 0.3-0.4; <0.001 for FI ≥0.4
Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) often coexist, worsening each other’s progression and contributing to poor outcomes. Frailty, a syndrome characterized by vulnerability to stressors, is highly prevalent in AF and HFpEF patients and has been associated with adverse outcomes such as stroke, hospitalization, and mortality. However, the specific prognostic implications of varying degrees of frailty in AF comorbid HFpEF patients remain unclear. This study investigates the relationship between frailty, measured using a deficit accumulation frailty index (FI), and adverse outcomes, particularly stroke, in this patient population. This post hoc analysis of the TOPCAT randomized control trial included 721 patients with AF and HFpEF from the Americas classified into three groups based on FI: Group 1 (FI < 0.3), Group 2 (FI 0.3–0.4), and Group 3 (FI ≥ 0.4). The primary outcome was stroke, and secondary outcomes included heart failure hospitalization, cardiovascular death, and all-cause mortality. Cox proportional hazards models and Kaplan–Meier analyses were used to assess the association between frailty status and outcomes. A dose–response relationship was evaluated using restricted cubic splines. 97.8% AF comorbid HFpEF patients were diagnosed frailty in this cohort. During a mean follow-up of 36 ± 19 months, stroke incidence was significantly higher in Groups 2 and 3 compared with Group 1 (adjusted HR for Group 2: 5.01 95% CI, 2.00–12.53; P = 0.001 and Group 3: 6.35 95% CI, 2.26–17.86; P < 0.001). A linear dose–response relationship between FI and stroke risk was observed. Higher frailty was also associated with increased cardiovascular and all-cause mortality but not significantly with heart failure hospitalization.
Zhou et al. (2026) conducted an RCT in Patients with atrial fibrillation comorbid with heart failure with preserved ejection fraction (HFpEF) (n=721). Higher frailty index scores increased stroke risk by over 5-fold (HR 5.01) for FI 0.3-0.4 and over 6-fold (HR 6.35) for FI ≥0.4 versus FI <0.3 in patients with AF and HFpEF during 36 months follow-up.