SGLT2i improves symptoms in HF across the range of LVEF

DEFINE-HF and PRESERVED-HF: Dapagliflozin improves heart failure symptoms and physical limitations across the entire range of LVEF

News - May 23, 2022

Presented at ESC Heart Failure 2022 by Mikhail Kosiborod, MD (Kansas City, MO, USA)

Introduction and methods

Improvement of symptoms and physical limitations is an important goal of treatment in patients with heart failure, regardless of their injection fraction. This pooled patient-level analysis of DEFINE-HF and PRESERVED-HF investigated the effect of dapagliflozin on these outcomes across the range of LVEF.

DEFINE-HF and PRESERVED-HF were both randomized, 12-week, double blind trials with dapagliflozin vs. placebo in patients with chronic HF, NYHA class ≥II and elevated NT-proBNP. DEFINE-HF included patients with EF ≤ 40% (n=263) and PRESERVED-HF included patients with EF ≥ 45% (n=324). In the pooled cohort (n=587), 43% were women, 33% African-American, 66% had a history of HF hospitalization and 37% had NYHA Class III-IV.

The primary endpoint was change in KCCQ Clinical Summary Score (CSS) at 12 weeks (adjusted for sex, baseline KCCQ, EF, AF, eGFR, and T2DM). The current analysis specifically explored whether the effects of dapagliflozin on health status were different across the range of LVEF. LVEF was assessed as a categorical variable (≤40%; >40% to <60%; ≥60%) and as a continuous variable.

Main results

  • At 12 weeks, a significant improvement in KCCQ-CSS was observed in the dapagliflozin group compared with the placebo group (effect size = 5.0; 95% CI 2.6-7.5 points; P < 0.0001). There was no evidence of heterogeneity of treatment benefit across LVEF categories (P for interaction = 0.79). There was also no evidence of treatment benefit modification by any of the other examined clinical or demographic characteristics.
  • When LVEF was examined as a continuous variable, the effects of dapagliflozin vs. placebo on change in KCCQ-CS at 12 weeks were consistent across the entire range of LVEF (P for interaction = 0.94).
  • Similar improvements were observed in KCCQ Physical Limitation Score (effect size = 5.0; 95% CI 1.8-8.2 points; P = 0.0023) KCCQ Total Symptom Score (5.0; 95% CI 2.3-7.7 points; P = 0.0003), and KCCQ Overall Summary Score (3.7; 95% CI 1.3-6.1; P = 0.003). Also here, benefits were consistent across the entire range of LVEF.
  • A KCCQ-CSS responder analysis showed that fewer patients on dapagliflozin vs. placebo had deterioration (> 5 points; OR 0.56; 95% CI 0.38-0.84; P = 0.0044) and more patients had at least small-moderate (≥ 5 points; OR 1.94; 95% CI 1.34-2.82; P = 0.0005), at least moderate-large (≥10 points; OR 2.26; 95% CI 1.48-3.44; P = 0.0002) and very large (≥20 points; OR 2.79; 95% CI 1.50-5.20; P = 0.0012) improvements in KCCQ-CSS. The treatment benefit was consistent across the entire range of LVEF.


This pooled patient-level analysis of DEFINE-HF and PRESERVED-HF showed that dapagliflozin vs. placebo improved symptoms and physical limitations across the entire range of LVEF.

Kosiborod stated: “Collectively, these results support the use of dapagliflozin in patients with HF regardless of ejection fraction”.

– Our coverage of ESC Heart Failure 2022 is based on the information provided during the congress –

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