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Severe Heart Failure and Treatment With Dapagliflozin Across the Ejection Fraction Spectrum: DAPA-HF and DELIVER
Riccardo M Inciardi1, Henri Lu2, Brian L Claggett3
1ASST Spedali Civili of Brescia, Department of Medical and Surgical Specialties, Radiologic Sciences and Public Health, University of Brescia, Brescia, Italy; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Insights
Patients with severe heart failure (HF) face higher cardiovascular risks. Dapagliflozin effectively reduced these risks across all ejection fraction levels, showing consistent safety and efficacy in this high-risk group.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Severe heart failure (HF) is linked to significant clinical symptoms, adverse cardiovascular (CV) outcomes, and increased mortality.
- Understanding the risk and treatment response in severe HF across the left ventricular ejection fraction (LVEF) spectrum is crucial.
Purpose of the Study:
- To determine the prevalence of severe HF.
- To assess the CV outcome risk in patients with severe HF.
- To evaluate the treatment response to dapagliflozin in severe HF patients across the LVEF spectrum using DAPA-HF and DELIVER trial data.
Main Methods:
- Severe HF was defined using ESC HFA criteria, including NYHA class III/IV, HF hospitalization within 12 months, and symptom burden.
- The primary endpoint was CV death or first worsening HF event.
- Treatment effects of dapagliflozin were analyzed based on severe HF status and LVEF.
Main Results:
- 6.7% of patients met the severe HF definition, with varying prevalence across LVEF subgroups.
- Patients with severe HF had a significantly higher risk of the primary endpoint (adjusted HR: 1.85).
- Dapagliflozin consistently reduced the primary endpoint risk regardless of severe HF status or LVEF, with a comparable safety profile.
Conclusions:
- Severe HF is associated with elevated CV event risk across the LVEF spectrum.
- Dapagliflozin demonstrated safety and efficacy in mitigating CV death or worsening HF in patients with severe HF.
Background:
Patients with severe heart failure (HF) experience debilitating clinical symptoms and worse cardiovascular (CV) outcomes with an excess mortality risk.
Objectives:
The authors aimed to assess the prevalence, CV outcome risk, and treatment response to the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin among patients with severe HF across the spectrum of left ventricular ejection fraction (LVEF) in DAPA-HF and DELIVER.
Methods:
Severe HF was adapted from the ESC (European Society of Cardiology) HFA (Heart Failure Association) definition: NYHA functional class III/IV, evidence of HF with reduced, mildly reduced, or preserved LVEF, HF hospitalization within the previous 12 months, and adverse patient-reported symptom burden (Kansas City Cardiomyopathy Questionnaire-Total Symptoms Score <75). Outcomes and the treatment effect of dapagliflozin were assessed for the primary endpoint of CV death or first worsening HF event by severe HF status.
Results:
Among 10,948 patients with available data to define severe HF, 730 (6.7%) fulfilled the severe HF definition (296/4,722 [6.2%] with LVEF ≤40%, 192/2,101 [9.1%] with LVEF 41%-49%, and 232/4,125 [5.6%] with LVEF ≥50%). Over a median follow-up of 22 months, the primary endpoint occurred in 231 patients, at a rate of 20 per 100 patient-years (Q1-Q3: 17-23 per 100 patient-years). Patients with severe HF experienced a higher rate of events than patients without severe HF (adjusted HR: 1.85; 95% CI: 1.60-2.12), regardless of LVEF (Pinteraction = 0.98). Treatment with dapagliflozin was consistently beneficial in reducing the risk of the primary endpoint regardless of severe HF status (Pinteraction = 0.48) across the LVEF spectrum (3-way Pinteraction = 0.52). The safety profile of dapagliflozin was also consistent regardless of the severe HF status.
Conclusions:
Severe HF was associated with an excess risk of CV events across the spectrum of LVEF. Treatment with the SGLT2i dapagliflozin appeared to be safe and effective in reducing the risk of CV death or worsening HF in this population. (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure [DAPA-HF]; NCT03036124; Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).
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