SGLT2 inhibitor therapy is fundamental in a wide range of heart failure management

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A new meta-analysis presented at Congress of the European Society of Cardiology 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 heart failure hospitalizations and improved survival and overall health when added to standard therapy in more than 20,000 patients with heart failure in 5 trials, including DELIVER and EMPEROR-Preserved.

“SGLT2 inhibitors reduced the risk of death and worsening of heart failure in a wide range of patients with heart failure, regardless of LVEF or care setting,” the author wrote. Study Scott D. Solomon, MD, Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School. “SGLT2 inhibitors have been shown to improve symptoms and confer clinically meaningful improvements in health-related quality of life, with benefits quickly seen within months of starting treatment.”

Guideline recommendations strongly support the use of SGLT2 inhibitors in heart failure patients with reduced ejection fraction, but have not yet established clinical benefit at higher ejection fraction. Solomon and colleagues performed a meta-analysis of DELIVER and EMPEROR-Preserved in heart failure patients with mildly reduced or preserved ejection fraction to address this knowledge gap.

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

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

In the 5 trials, 21,947 participants were included. People in heart failure trials with reduced ejection fraction were more often younger and male than those in heart failure trials with mildly reduced or preserved ejection fraction.

Data from 12,251 DELIVER and EMPEROR-Preserved participants suggest that SGLT2 inhibitors reduced composite cardiovascular mortality or first hospitalization for heart failure (relative risk [HR], 0.80; 95% CI, 0.73, 0.87), with no evidence of heterogeneity.

Additionally, results were consistent across all endpoints, 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 mortality (HR, 0.97; 95% CI, 0.88, 1.06).

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

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

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

“This comprehensive meta-analysis supports the role of SGLT2 inhibitors as a foundational therapy in the management of heart failure, regardless 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.

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