Ejection Fraction and Effect of Empagliflozin in Heart Failure
Quick Takes
- SGLT2 inhibition is beneficial in HF patients regardless of EF, except in patients with an LVEF ≥65%. (This subgroup represented <10% of the entire patient population and the total number of events. And therefore, estimates for this subgroup are not necessarily precise. Additional studies in this subgroup are needed to clarify the true effect of empagliflozin.)
- The benefits of SGLT2 inhibitors are that they are mainly from reducing HF hospitalizations rather than mortality.
Study Questions:
What is the impact of ejection fraction (EF) on the effect of the sodium–glucose cotransporter 2 (SGLT2) inhibitor empagliflozin on heart failure (HF) outcomes?
Methods:
The study investigators performed a pooled analysis on both the EMPEROR-Reduced and EMPEROR-Preserved trials (9,718 patients; 4,860 empagliflozin and 4,858 placebo), and patients were grouped based on EF: <25% (n = 999), 25–34% (n = 2,230), 35–44% (n = 1,272), 45–54% (n = 2,260), 55–64% (n = 2,092), and ≥65% (n = 865). The median duration of follow-up was 21 months. The outcomes they assessed included: 1) the primary endpoint of time to HF hospitalization or cardiovascular death, 2) time to first HF hospitalization, and 3) time to cardiovascular death (the components of the primary endpoint); 4) total (first and recurrent) HF hospitalization (the first secondary endpoint), and 5) the change in Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score at 52 weeks.
Results:
The study investigators found that the risk of cardiovascular death and hospitalization for HF declined progressively as EF increased from <25% to ≥65%. Empagliflozin reduced the risk of cardiovascular death or HF hospitalization, mainly by reducing HF hospitalizations. Empagliflozin reduced the risk of HF hospitalization by 30% in all EF subgroups, with an attenuated effect in patients with an EF ≥65% (see Structured Graphical Abstract from the article).
Hazard ratios and 95% confidence intervals were: EF <25%: 0.73 (0.55–0.96); EF 25–34%: 0.63 (0.50–0.78); EF 35–44%: 0.72 (0.52–0.98); EF 45–54%: 0.66 (0.50–0.86); EF 55–64%: 0.70 (0.53–0.92); and EF ≥65%: 1.05 (0.70–1.58). Other HF outcomes and measures, including KCCQ, showed a similar response pattern. Gender did not influence the responses to empagliflozin.
Conclusions:
The study authors concluded that the magnitude of the effect of empagliflozin on HF outcomes was clinically meaningful and similar in patients with EFs <25% to <65%, but was attenuated in patients with an EF ≥65%.
Perspective:
This is an important study because it suggests that SGLT2 inhibition is beneficial in HF patients regardless of EF, except in patients with an LVEF ≥65%. (This subgroup represented <10% of the entire patient population and the total number of events. And therefore, estimates for this subgroup are not necessarily precise. Additional studies in this subgroup are needed to clarify the true effect of empagliflozin.) Another key takeaway regarding the benefits of SGLT2 inhibitors is that they are mainly from reducing HF hospitalizations rather than mortality. We need therapies/medications that will make a substantial improvement in survival!
Clinical Topics: Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure
Keywords: Cardiomyopathies, Geriatrics, Glucosides, Heart Failure, Hospitalization, Outcome Assessment, Health Care, Risk Assessment, Secondary Prevention, Sodium-Glucose Transporter 2 Inhibitors, Stroke Volume, Ventricular Function, Left
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