Reduced Risk for Cardiac Death With SGLT-2 Inhibitor Use in HFrEF, but Not in HFpEF

The beneficial effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on outcomes of cardiac mortality are associated with type of heart failure (HF), with the agents shown to reduce the risk for cardiac death among patients with HF with preserved ejection fraction (HFpEF) but not those with HF with reduced EF (HFrEF). These findings were published in the journal Diabetes Research and Clinical Practice.

The researchers conducted a meta-analysis to evaluate the effectiveness of SGLT-2 inhibitors in patients with different types of HF. They performed a literature search of randomized controlled trials (RCTs) that compared SGLT-2 inhibitors with placebo in patients with HF. For evidence synthesis, they used a random-effects model. The primary study endpoint was cardiac death. Secondary endpoints included the composite outcome of cardiac death or rehospitalization because of HF (HHF) and the individual outcome of HHF.

Studies were included in the meta-analysis, based on the following criteria: the intervention group was treated with SGLT inhibitors, that is, empagliflozin, dapagliflozin, sotagliflozin, canagliflozin, or ertugliflozin; patients in the control group received a placebo or other hypoglycemic agent; the study sample included patients with HF; the studies were RCTs; and the studies were published in English. A total of 13 studies were included in the meta-analysis, 12 of which were RCTs.

In patients with HFpEF, SGLT-2 inhibitors were shown to reduce the composite endpoint of cardiac death or HHF (hazard ratio [HR], 0.78; 95% CI, 0.70-0.87;

P <.001) and that of HHF (HR, 0.74; 95% CI, 0.64-0.85; P <.001), but not that of cardiac death (HR, 1.01; 95% CI, 0.80-1.28; P =.943).

In contrast, in patients with HFrEF, SGLT-2 inhibitors decreased the composite endpoint of cardiac death or HHF (HR, 0.75; 95% CI, 0.69-0.82; P <.001) and the individual endpoints of cardiac death (HR, 0.84; 95% CI, 0.75-0.95; P =.007) and HHF (HR, 0.69; 95% CI, 0.62-0.77; P <.001).

The current study has several limitations. Although it assessed the safety and efficacy of SGLT-2 inhibitors in patients with different types of HF, the number of studies included in the meta-analysis was too small to evaluate publication bias. Further, a smaller number of studies and participants contributed data to the HFpEF subgroup than to the HFrEF subgroup. Additionally, regression analysis was not conducted to evaluate the link between population characteristics and clinical outcomes, since the number of studies included was small.

“The benefits of SGLT-2 inhibitors on the outcome of cardiac death are related to the type of HF. SGLT-2 inhibitors reduced the risk of cardiac death in patients with HFrEF but not in those with HFpEF,” the study authors wrote.

Disclosure: None of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies.  

Reference

Zhao L, Guo W, Huang W, Wang L, Huang S. Benefit of sodium-glucose cotransporter-2 inhibitors on survival outcome is related to the type of heart failure: a meta-analysis.Diabetes Res Clin Pract. Published online April 10, 2022. doi:10.1016/j.diabres.2022.109871