Objective:

To compare the efficacy and safety of quadruple therapy versus triple therapy in patients with heart failure and preserved ejection fraction (HFpEF).

Approach:

• Study Design: A single-center retrospective cohort study including 600 patients with HFpEF receiving triple therapy, utilizing a 1:1 propensity score matching approach.
• Primary Endpoint: The primary endpoint was the composite of heart failure hospitalization or cardiovascular death.

Key Findings:

• Quadruple therapy group had a significantly lower incidence of the primary endpoint compared to the triple therapy group (17.8% vs. 25.0%, hazard ratio (HR) = 0.678, 95% confidence interval (CI): 0.432–0.967, P = 0.035).
• First heart failure hospitalization rates were lower in the quadruple therapy group (14.4% vs. 20.6%, HR = 0.672, P = 0.030).
• Recurrent heart failure hospitalization rates were also lower in the quadruple therapy group (0.217 vs. 0.325 events per person-year, HR = 0.654, P = 0.015).
• Subgroup analyses indicated greater benefits from quadruple therapy in patients with concomitant coronary artery disease (HR = 0.591, P = 0.047) and higher baseline heart rates (HR = 0.572, P = 0.045).

Interpretation:

Quadruple therapy was associated with a lower risk of heart failure hospitalization or cardiovascular death compared to triple therapy.

Limitations:

• The observational design limits the ability to establish causality.
• Findings require prospective validation.

Conclusion:

Quadruple therapy may reduce heart failure hospitalizations in patients with HFpEF, especially in those with coronary artery disease and higher heart rates.