Empagliflozin: Preventing new-onset anemia in heart failure patients with reduced ejection fraction

By Samar Mahmoud, MS
Published January 26, 2022

Key Takeaways

  • This randomized, double-blind, placebo-controlled study found that anemia was associated with poor outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF). 

  • Regardless of anemia status at baseline, empagliflozin, a sodium–glucose co-transporter 2 inhibitor, reduced new-onset anemia and improved heart failure as well as kidney outcomes, supporting the clinical use of empagliflozin to correct anemia.

Anemia is a common comorbidity in patients with HF and HFrEF and is associated with lower quality of life and worse outcomes, including increased risk of fatal events.

Why This Study Matters

Recent studies have suggested that correcting anemia might not be sufficient to improve outcomes in patients with HFrEF and that the mechanism by which anemia is corrected may be more important. To shed light on the potential of empagliflozin to correct anemia, researchers investigated its impact on haematocrit as well as its ability to reduce cardiovascular mortality.

Study Design

Patients in the study were enrolled in the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR-Reduced) if they had chronic HF with a left ventricular ejection fraction ≤ 40%. Study participants were randomly assigned to receive either placebo or 10 mg daily of empagliflozin in addition to their daily medications. 

The primary endpoint of the study was the composite endpoint of cardiovascular death or hospitalization for HF and was analyzed as the time to first event. Hematocrit and hemoglobin were measured at baseline as well as during follow-up visits and anemia was defined by hematocrit levels <39% in men or <36% in women. 

Results and Conclusions

The presence of anemia was associated with an increased risk of cardiovascular and all-cause mortality as well as total HF hospitalizations and worse kidney outcomes. 

In comparison to the placebo group,  empagliflozin led to a rapid increase in hematocrit and hemoglobin levels and reduced the percentage of patients with anemia, with a difference of 8.5% at week 52. 

Similarly, empagliflozin led to a reduction in the number of patients with new-onset anemia, with 22.6% of participants in the placebo group developing anemia during follow-up compared to 12.3% in the empagliflozin group.  Regardless of anemia status at baseline, empagliflozin improved HF and kidney outcomes. 

Related Research

Consider these findings from similar research studies:

  • In patients with iron deficiency, treatment with ferric carboxymaltose reduced risk of hospitalization due to heart failure but had no effect on risk of cardiovascular death (Source). 

  • Empagliflozin reduced risk of cardiovascular death or hospitalization for heart failure, irrespective of diabetes status (Source).

Original Source 

Ferreira JP, Anker SD, Butler J, et al. Impact of anaemia and the effect of empagliflozin in heart failure with reduced ejection fraction: findings from EMPEROR‐ Reduced. European J of Heart Fail. Published online January 9, 2022:ejhf.2409.

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