medwireNews: Empagliflozin reduces the risk for adverse cardiovascular outcomes in people with heart failure and a reduced ejection fraction irrespective of their baseline glycated hemoglobin (HbA1c) level, EMPEROR-Reduced trial data show.
Based on their findings, Stefan Anker (Charité Universitätsmedizin Berlin, Germany) and colleagues say: “Decisions regarding the use of empagliflozin for the treatment of heart failure and a reduced ejection fraction should not be driven by the glycemic status of individual patients.”
The primary analysis of the EMPEROR-Reduced trial, reported previously by medwireNews, showed that empagliflozin 10 mg/day significantly improved cardiovascular and renal outcomes in 3730 patients with chronic heart failure (class II–IV) and a left ventricular ejection fraction of 40% or lower relative to placebo.
The current, prespecified analysis compared the findings among 1856 individuals with diabetes (50%), 1268 with prediabetes (34%), and 606 with normoglycemia (16%).
The researchers report in Circulation that the rate of the primary composite outcome of cardiovascular death or hospitalization for heart failure in people with diabetes was significantly lower in the empagliflozin group than in the placebo group, at 21.6% versus 28.5%, corresponding to a significant hazard ratio (HR) of 0.72 in favor of empagliflozin.
The rate was also significantly lower with versus without empagliflozin in the people without diabetes, at 17.2% versus 21.0% and a HR of 0.78.
Notably, there was no significant difference in the impact of empagliflozin between the people with and without diabetes and “the effects of the drug did not differ in patients with prediabetes or normoglycemia,” Anker et al remark.
Furthermore, baseline HbA1c did not significantly alter the benefits of empagliflozin on the primary outcome when analyzed as a continuous variable.
A similar pattern was seen for the composite renal endpoint, defined as the need for chronic dialysis or renal transplant, a 40% or greater decrease in estimated glomerular filtration rate (eGFR), or a sustained eGFR below 15 mL/min per 1.73 m2 if the baseline eGFR was at least 30 mL/min per 1.73 m2 or below 10 mL/min per 1.73 m2 if the baseline eGFR was below 30 mL/min per 1.73 m2.
The HR for this endpoint was 0.53 with versus without empagliflozin in the people with diabetes and 0.42 in those without diabetes. And again, there was no significant treatment-by-diabetes interaction.
Anker and team conclude: “These findings strongly underscore the conclusion that the benefits of empagliflozin on the heart and the kidneys are not related to the level of dysglycemia or to changes in glycated hemoglobin.”
They add: “The precise mechanism of action of SGLT2 inhibitors to lower the risk of heart failure events remains to be defined, but given our findings, the pathophysiologic abnormalities that are ameliorated by empagliflozin are not dependent on or are likely to be meaningfully influenced by abnormalities in blood glucose.”
The investigators also note that their findings are in line with those of the DAPA-HF trial, and taken together, the results of the two trials “reinforce a new role for SGLT2 inhibitors in patients with heart failure and a reduced ejection fraction, independent of diabetes or the baseline level of glycated hemoglobin.”
The study findings were also presented at the virtual AHA Scientific Sessions 2020.
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