SGLT2i plus low-dose triple therapy had a significantly higher risk of CV death and heart failure hospitalization than high-dose triple therapy in HFrEF (adjusted HR 4.10; 95% CI 2.07-8.13; p<0.001).
Cohort (n=334)
Does SGLT2i combined with low-dose conventional triple therapy improve cardiovascular outcomes compared to high-dose conventional triple therapy in patients with HFrEF?
In patients with HFrEF, adding an SGLT2 inhibitor to low-dose conventional triple therapy is associated with worse clinical outcomes compared to high-dose conventional triple therapy, highlighting the importance of optimizing background GDMT doses.
Effect estimate: adjusted HR 4.10 (95% CI 2.07-8.13)
p-value: p=<0.001
Background and Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular (CV) death and heart failure hospitalizations (HFH) in patients with heart failure with reduced ejection fraction (HFrEF). However, data regarding their use in combination with different doses of guideline-directed medical therapy (GDMT) remain limited. This study aimed to evaluate whether SGLT2i combined with low-dose conventional triple therapy is non-inferior to high-dose conventional triple therapy in preventing adverse cardiovascular outcomes. Materials and Methods: This retrospective observational study included 334 patients with HFrEF treated between 31 March 2018 and 31 March 2024. Of these, 110 received SGLT2i plus low-dose conventional triple therapy, and 224 received high-dose conventional triple therapy. A non-inferiority framework was applied to compare outcomes between groups. The primary endpoint was a composite of CV death and HFH, while secondary endpoints included the individual components. Results: The composite endpoint occurred more frequently in the SGLT2i plus low-dose group. After inverse probability of treatment weighting and multivariable Cox analysis, this group demonstrated a significantly higher risk of the composite outcome (adjusted HR 4.10, 95% CI 2.07–8.13; p < 0.001). CV death was similar between groups; however, HFH was significantly more frequent in the SGLT2i plus low-dose group. Conclusions: In patients with HFrEF, SGLT2i combined with low-dose conventional triple therapy did not demonstrate comparable clinical outcomes to high-dose conventional triple therapy in reducing CV death and HFH, particularly in patients with a higher baseline burden of disease severity. These findings underscore the importance of optimizing background GDMT dosing alongside the incorporation of SGLT2i into clinical practice.
Khamboonruang et al. (Fri,) conducted a cohort in Heart Failure with Reduced Ejection Fraction (HFrEF) (n=334). SGLT2i plus low-dose conventional triple therapy vs. high-dose conventional triple therapy was evaluated on composite of CV death and HFH (adjusted HR 4.10, 95% CI 2.07-8.13, p=<0.001). SGLT2i plus low-dose triple therapy had a significantly higher risk of CV death and heart failure hospitalization than high-dose triple therapy in HFrEF (adjusted HR 4.10; 95% CI 2.07-8.13; p<0.001).