Meta-analysis supports mortality reduction with SGLT2 inhibition in HF
medwireNews: A meta-analysis of the DAPA-HF and EMPEROR-Reduced trials supports use of sodium-glucose cotransporter (SGLT)2 inhibitors in people with heart failure (HF) with or without diabetes, and suggests a positive effect on mortality endpoints.
“The two trials enrolled overlapping and complementary patient populations, which spanned the broad spectrum of patients with HF [with reduced ejection fraction] seen in clinical practice,” write the researchers in The Lancet.
Across the two trials, involving 8474 patients who had HF with reduced ejection fraction, treatment with an SGLT2 inhibitor (dapagliflozin in DAPA-HF and empagliflozin in EMPEROR-Reduced) resulted in a significant 13% reduction in all-cause mortality and a 14% reduction in cardiovascular (CV) mortality.
“The modest size of the cardiovascular death benefit might explain why it is observed inconsistently in individual trials,” suggest Faiez Zannad (Centre Hospitalier Régional Universitaire de Nancy, France) and study co-authors.
They note that reduction in risk for CV mortality across various SGLT2 inhibitor trials has ranged from a nonsignificant 2% to a significant 38%.
There was also a 26% reduction in the trials’ primary endpoint of HF hospitalization or CV death, and a 38% reduction in a composite renal outcome of a 50% or higher sustained decline in estimated glomerular filtration rate (eGFR), end-stage renal disease, or renal death.
“Our meta-analysis established a solid evidence base supporting an important role of empagliflozin and dapagliflozin primarily to reduce hospitalisations for heart failure and, secondarily, to improve renal outcomes and decrease all-cause and cardiovascular death,” write the researchers.
They add: “Such a combination of benefits is unique among available drugs for heart failure.”
From the subgroup analyses, the team highlights the consistent benefits seen for trial participants with reduced kidney function. The risk for the primary endpoint was reduced a significant 23% in those with an eGFR below 60 mL/min per 1.73 m2, which “provides evidence of an important reduction of cardiovascular death or hospitalisation for heart failure in this high-risk subgroup,” say Zannad et al.
But they also caution that their analysis suggested a weaker effect of SGLT2 inhibition in patients with more severe HF (New York Heart Association class III–IV) versus those with milder symptoms, in people with White versus Black or Asian ethnicity, and in people enrolled in Europe versus other regions.
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