SGLT2 Inhibitor Therapy Foundational in Wide Range of Heart Failure Management

Scott D. Solomon, MD

A new meta-analysis presented at the European Society of Cardiology Congress 2022 supported the role of SGLT2 inhibitors as foundational therapies in the management of heart failure.

The therapies significantly reduced the risk of cardiovascular death and hospitalizations for heart failure and improved survival and overall health status when added to standard therapy in more than 20,000 patients with heart failure across 5 trials, including DELIVER and EMPEROR-Preserved.

“SGLT2 inhibitors reduced the risk of mortality and worsening heart failure across a broad range of patients with heart failure, irrespective of LVEF or care setting,” wrote study author Scott D. Solomon, MD, Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School. “SGLT2 inhibitors were shown to ameliorate symptoms and confer clinically meaningful improvements in health related quality of life, with benefits seen rapidly within months of treatment initiation.”

Guideline recommendations strongly support the use of SGLT2 inhibitors in patients with heart failure with reduced ejection fraction, but have yet to establish clinical benefit at higher ejection fraction. Solomon and colleagues performed a meta-analysis of DELIVER and EMPEROR-Preserved in patients with heart failure with mildly reduced or preserved ejection fraction to close this knowledge gap.

They extended the meta-analysis to include patients with reduced ejection fractions (DAPA-HF and EMPEROR-Reduced) and individuals admitted to hospital with worsening heart failure, irrespective of ejection fraction (SOLOIST-WHF). Based on the 5 placebo-controlled trials, the team determined the effects of SGLT2 inhibitors on heart failure hospitalization, mortality outcomes, and overall health status.

They identified the primary endpoint of the meta-analysis as a composite of time to cardiovascular death or first hospitalization for heart failure and investigators assessed heterogeneity in effect of treatment across various subgroups of interest.

Across the 5 trials, 21,947 participants were included. Individuals in trials of heart failure with reduced ejection fraction were more frequently younger and male, compared to those enrolled in trials of heart failure with mildly reduced or preserved ejection fraction.

Data on the 12,251 participants from DELIVER and EMPEROR-Preserved suggest SGLT2 inhibitors reduced composite cardiovascular death or first hospitalization for heart failure (hazard ratio [HR], 0.80; 95% CI, 0.73 - 0.87), without evidence of heterogeneity.

Moreover, the findings were consistent across endpoint components, including cardiovascular death (HR, 0.88; 95% CI, 0.77 - 1.00) and first hospitalization for heart failure (HR, 0.74; 95% CI, 0.67 - 0.83). There was no significant effect on all-cause death (HR, 0.97; 95% CI, 0.88 - 1.06).

Investigators noted any serious adverse event occurred less frequently in SGLT2 inhibitor groups compared with placebo in both trials, despite the inability to perform a direct comparison.

Data from all 5 trials suggest treatment with SGLT2 inhibitors reduced the risk of composite cardiovascular death or hospitalization for heart failure (HR, 0.77; 95% CI, 0.72 - 0.82), as well as cardiovascular death (HR, 0.97; 95% CI, 0.79 - 0.95) and death from any cause (HR, 0.92; 95% CI, 0.86 - 0.99).

Efficacy of SGLT2 inhibitors on the composite of cardiovascular death or first hospitalization for heart failure was consistent across each studied subgroup, including patients with left ventricular ejection fraction greater than 60%.

“This comprehensive meta-analysis supports the role of the SGLT2 inhibitors as a foundational therapy in the management of heart failure, irrespective of ejection fraction or care setting,” Solomon concluded.

The study, “SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomized controlled trials,” was published in The Lancet.