Digoxin use and heart failure hospitalization in patients with heart failure with preserved ejection fraction: a real-world retrospective analysis

Background

Heart failure with preserved ejection fraction (HFpEF) represents a heterogeneous clinical syndrome with limited evidence-based treatment options. In routine clinical practice, digoxin continues to be used in selected HFpEF patients, particularly those with atrial fibrillation and advanced symptoms, despite uncertainty regarding its long-term clinical effects in this population.

Purpose

To investigate the real-world impact of digoxin therapy on heart failure hospitalization rates in patients with HFpEF.

Methods

This retrospective, real-world study included patients with heart failure with preserved ejection fraction who were followed at a tertiary care center. Patients were classified according to digoxin use at baseline. Baseline demographic, clinical, echocardiographic, laboratory, and treatment characteristics were recorded. The primary outcome was heart failure hospitalization within one year. Event-free survival was assessed using Kaplan–Meier analysis and compared with the log-rank test. Cox proportional hazards regression was performed to identify factors associated with heart failure hospitalization after adjustment for relevant clinical covariates. NT-proBNP exhibited a skewed distribution and was therefore log-transformed before inclusion in the Cox proportional hazards regression models.

Results

total of 462 patients with HFpEF were included, of whom 59 (12.8%) were receiving digoxin at baseline. Compared with patients not receiving digoxin, those treated with digoxin had a higher-risk clinical profile. They were older and had a markedly higher prevalence of atrial fibrillation, higher body mass index, and more advanced symptoms, with a greater proportion of patients in NYHA class III–IV (all p<0.05). Markers of cardiac stress and congestion were also more pronounced in the digoxin group, including significantly higher left atrial volume index, NT-proBNP, and C-reactive protein levels (Table 1).

Despite these unfavorable baseline characteristics, heart failure hospitalization rates at one year were similar between the digoxin and non-digoxin groups (57.6% vs. 60.3%, p=0.785). Kaplan–Meier analysis demonstrated no significant difference in freedom from heart failure hospitalization between groups during follow-up (log-rank p=0.247) (Figure 1).

In multivariable Cox regression analysis, digoxin use was not independently associated with heart failure hospitalization (adjusted HR 0.75, 95% CI 0.50–1.12; p=0.155). In contrast, NYHA functional class and log-transformed NT-proBNP emerged as the strongest independent predictors of hospitalization risk.

Conclusion

In this real-world HFpEF cohort, digoxin use was not independently associated with heart failure hospitalization despite a higher baseline risk profile. These findings support the neutral long-term safety of digoxin in selected HFpEF patients, particularly those with atrial fibrillation.For image description, please refer to the figure legend and surrounding text.FigureFor image description, please refer to the figure legend and surrounding text.