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Effect of Empagliflozin in Patients With Heart Failure
Quick Takes
- In a patient-level pooled analysis from two large trials, empagliflozin lowered risk for HF hospitalization, number of HF hospitalizations, and Kansas City Cardiomyopathy Questionnaire score to a similar extent across a wide range of EF ranging from <25% to <65%.
- Its impact was attenuated in patients with EF ≥65%.
- The impact of empagliflozin did not vary by sex.
Study Questions:
What is the effect of empagliflozin on heart failure (HF) hospitalizations across the full range of left ventricular ejection fractions (LVEFs)?
Methods:
This was a pooled analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials. Both were randomized, placebo-controlled trials that evaluated efficacy of empagliflozin compared to placebo in HF patients. EMPEROR-Reduced enrolled patients with EF ≤40% and EMPEROR-Preserved enrolled patients with EF >40%. Outcomes of interest included: 1) time to HF hospitalization or cardiovascular death, 2) time to first HF hospitalization, 3) time to cardiovascular death, 4) total HF hospitalizations, and 5) change in Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score at 52 weeks. Patients were divided into six groups based on EF: <25%, 25-34%, 35-44%, 45-54%, 55-64%, and ≥65%.
Results:
The two trials enrolled 9,718 patients followed-up for a median of 21 months. With increasing EF, patients were more likely to be older and female; to have impaired renal function and lower B-type natriuretic peptide; and to have lower use of angiotensin antagonists, beta-blockers, and mineralocorticoid receptor antagonists. In the placebo group, the risk for HF hospitalization or cardiovascular death lowered progressively with increasing EF. Empagliflozin lowered the composite of HF hospitalization and cardiovascular death by predominantly lowering HF hospitalization. It lowered both time to HF hospitalization and total number of HF hospitalizations by about 25-35% across all EF subgroups with an attenuated effect for patients with EF ≥65%. A similar pattern of effects was seen for other outcomes, including KCCQ scores as well. This response was not different by sex.
Conclusions:
In a patient-level pooled analysis of two large, randomized trials in HF patients with both reduced and preserved EF, empagliflozin reduced time to HF hospitalization and number of HF hospitalizations similarly across all EF subgroups ranging from <25% to <65%. The effect was attenuated among patients with EF >65%.
Perspective:
Several trials with neurohormonal antagonists have shown a linear response between EF and treatment effects. These agents show the largest benefit among patients with EF <30% and attenuated benefits with EF >50%. In comparison, this pooled analysis from two large trials conducted with empagliflozin in patients with HF with reduced and preserved EF, the drug lowered hazard for HF hospitalization to a similar extent among patients with EF ranging from <25% to <65%. Impact on other endpoints such as number of HF hospitalizations and KCCQ score showed a similar trend. Furthermore, this efficacy was similar for both men and women. However, its efficacy was blunted for patients with EF ≥65%. With limited therapies available for patients with HF with preserved EF, results from this study support using SGLT2 inhibitors as first line of therapy.
Clinical Topics: Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Adrenergic beta-Antagonists, Angiotensins, Cardiomyopathies, Heart Failure, Hospitalization, Mineralocorticoid Receptor Antagonists, Natriuretic Peptide, Brain, Sodium-Glucose Transporter 2 Inhibitors, Stroke Volume, Ventricular Function, Left
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