Article Impact Level: HIGH Data Quality: STRONG Summary of Circulation, 0(0), 10.1161/CIRCULATIONAHA.122.059785. https://doi.org/10.1161/CIRCULATIONAHA.122.059785 Dr. Gerasimos Filippatos et al
Points
- Empagliflozin treatment reduced the risks of CVD or first HF hospitalization (HR 0.79 for patients with diabetes vs HR 0.78 for those without diabetes) as a primary outcome, as well as total HF hospitalizations and estimated glomerular filtration rate decline regardless of glycemic status at baseline.
- Empagliflozin also did not increase hypoglycemic events risk in patients with and without diabetes.
- Empagliflozin remained robust in its effects on HF-pEF patients regardless of baseline glycemic status.
Summary
Empagliflozin has been established as one of the possible key treatments for patients with heart failure with a preserved ejection fraction (HF-pEF). This study, on the other hand, attempts to address gaps in our understanding with it comes to empagliflozin’s consistency of effectiveness in patients with and without diabetes.
To examine this, this secondary analysis of the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trial examined patients (n = 5,988) with heart failure categorized through classes II and IV together with a >40% left ventricular ejection fraction. Standard therapy was administered to these patients alongside either 10 mg of empagliflozin or a placebo. The primary outcome considered was the first hospitalization for heart failure or cardiovascular death (CVD).
Around 2,938 patients (49%) total had diabetes among all patients under the study; under this group, the risk of primary outcome, HF hospitalizations, and estimated glomerular filtration rate decline was higher. Meanwhile, empagliflozin treatment reduced the primary outcome rate irrespective of diabetes status (HR 0.79 [95% CI, 0.67, 0.94] for patients with diabetes vs. HR 0.78 [95% CI, 0.64, 0.95] in patients without diabetes; Pinteraction = 0.92). Empagliflozin also consistently reduced total HF hospitalizations in patients with and without diabetes. Alongside this, the attenuation of estimated glomerular filtration rate decline was also observed in double-blind empagliflozin treatment effects in patients both with and without diabetes; this was, however, more pronounced in those with diabetes (1.77 in diabetes versus 0.98 mL/min per 1.73 m2 in patients without diabetes; Pinteraction = 0.01). Across all three endpoints, differences between empagliflozin effects were negligible in patients with prediabetes or normoglycemia (33% and 18% of the patient population, respectively). Additionally, baseline hemoglobin A1c did not change primary outcome effects when examined as a continuous variable (Pinteraction = 0.26). No risk increase of hypoglycemic events was observed in either subgroup compared to placebo.
In conclusion, HF-pEF patients under the EMPEROR-Preserved trial experienced a significantly reduced HF outcomes risk due to empagliflozin treatment, irrespective of diabetes status as a baseline.
Link to the article: https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.122.059785
References Filippatos, G., Butler, J., Farmakis, D., Zannad, F., Pernille Ofstad, A., Pedro Ferreira, J., Green, J. B., Rosenstock, J., Schnaidt, S., Brueckmann, M., Pocock, S. J., Packer, M., Anker, S. D., & null, null. (n.d.). Empagliflozin for heart failure with preserved left ventricular ejection fraction with and without diabetes. Circulation, 0(0), 10.1161/CIRCULATIONAHA.122.059785. https://doi.org/10.1161/CIRCULATIONAHA.122.059785
