Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure

RCT (n=3730) found among patients receiving recommended therapy for heart failure, those in empagliflozin group had lower risk of CV death or hospitalisation for heart failure (primary outcome) than those in placebo group, regardless of the presence or absence of diabetes.

SPS commentary:

In the EMPEROR-Reduced Trial, over a median of 16 months, a primary outcome event (composite of CV death or hospitalisation for worsening heart failure) occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio 0.75; 95% CI; 0.65 to 0.86; p<0.001).


According to an editorial, similar findings were reported in DAPA-HF study of dapagliflozin and again, the benefit was seen regardless of diabetes status. It notes  that in both DAPA-HF and EMPEROR-Reduced, the two components of the primary outcome were analysed individually but were not formally tested for significance. In DAPA-HF, the hazard ratio for cardiovascular death considered alone was 0.82 (95% CI, 0.69 to 0.98), a result that is nominally significant. In contrast, in EMPEROR-Reduced, the hazard ratio for cardiovascular death alone was 0.92 (95% CI, 0.75 to 1.12), a result that is not nominally significant. It discusses whether this apparent difference in the effect on cardiovascular death real and a definitive answer to this question would likely require a head-to-head randomized trial. It concludes that the results of the EMPEROR-Reduced trial confirm that the findings in DAPA-HF were no fluke and substantially strengthen the rationale for the use of SGLT2 inhibitors in patients with heart failure and a reduced ejection fraction. It alludes to the Canadian Cardiovascular Society and the Canadian Heart Failure Society who have recommended the use of SGLT2 inhibitors in patients with mild or moderate heart failure with an ejection fraction of 40% or less to improve symptoms and quality of life and to reduce the risk of hospitalization and cardiovascular mortality. It suggests  the EMPEROR-Reduced data will provide further impetus for other groups to address this question.


A meta-analysis in the Lancet noted that the effects of empagliflozin and dapagliflozin on hospitalisations for heart failure were consistent in the two independent trials and suggest that these agents also improve renal outcomes and reduce all-cause and cardiovascular death in patients with heart failure with reduced ejection fraction.


New England Journal of Medicine

Resource links:


Meta-analysis of the EMPEROR-Reduced and DAPA-HF trials