Este documento presenta los resultados de un meta-análisis pre-especificado de los estudios DELIVER y EMPEROR-Preserved que evaluaron la efectividad de los inhibidores de SGLT2 en pacientes con insuficiencia cardíaca con fracción de eyección preservada. Los resultados mostraron una reducción del 20% en el riesgo combinado de muerte cardiovascular o hospitalizaciones por insuficiencia cardíaca con los SGLT2. Esta meta-análisis confirma que los SGLT2 reducen de manera robusta la muerte cardiovascular y las hospitaliz

1. Martina Amiguet Comins
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Pre-specified meta-analysis
of DELIVER and EMPEROR-Preserved
Presentación del ESC Congress 2022
https://doi.org/10.1016/S0140-6736(22)01429-5
Pre-Specified Meta-Analysis of
DELIVER and EMPEROR-Preserved
Dapagliflozin Evaluation to improve
the LIVEs of patients with PReserved
Ejection Fraction Heart Failure
DELIVER
Empagliflozin in Heart Failure with a
Preserved Ejection Fraction
EMPEROR-PRESERVED
+

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Presentación del ESC Congress 2022
https://doi.org/10.1016/S0140-6736(22)01429-5
Pre-specified meta-analysis
of DELIVER and EMPEROR-Preserved

3. Martina Amiguet Comins
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Presentación del ESC Congress 2022
https://doi.org/10.1016/S0140-6736(22)01429-5
Pre-specified meta-analysis
of DELIVER and EMPEROR-Preserved
18% 21%
NNT= 32 NNT= 31
EMPEROR-PRESERVED and DELIVER were not individually powered to test de effect of de SGLT2i on CV mortality
Background SGLT2i have shown benefit in CVD, HF irrespective of LVEF and CKD, regardless of diabetes status.

4. Martina Amiguet Comins
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Presentación del ESC Congress 2022
https://doi.org/10.1016/S0140-6736(22)01429-5
Pre-specified meta-analysis
of DELIVER and EMPEROR-Preserved
Background Study Population

5. Martina Amiguet Comins
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Presentación del ESC Congress 2022
https://doi.org/10.1016/S0140-6736(22)01429-5
Pre-specified meta-analysis
of DELIVER and EMPEROR-Preserved
Background Study Population

6. Martina Amiguet Comins
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Presentación del ESC Congress 2022
https://doi.org/10.1016/S0140-6736(22)01429-5
Pre-specified meta-analysis
of DELIVER and EMPEROR-Preserved
Background “Are DELIVER and EMPEROR-PRESERVED twins?”
DELIVER EMPEROR-Preserved
Interventions Dapagliflozin 10 mg daily or placebo (1:1) Empagliflozin 10 mg daily or placebo (1:1)
Patient population
• ≥40 years of age with symptomatic NYHA Class II-IV HF at
enrollment and typical signs/symptoms of HF ≥6 weeks before
enrollment with at least intermittent need for diuretic treatment
• LVEF >40% and evidence of structural heart diseasea within 12
months (+IMPROVED LVEF)
• Elevated NT-proBNP levels
• eGFRb ≥25 mL/min/1.73 m2
• Ambulatory or hospitalized off IV HF therapy for ≥24 hours
• ≥18 years of age (Japan: ≥20 years of age) with NYHA Class II-IV HF for ≥3
months and oral diuretic dose stable for ≥1 week, if prescribed
• LVEF >40%
• Structural heart diseasea within 6 months or hHF within 12 months
• Elevated NT-proBNP levels
• eGFRb ≥20 mL/min/1.73 m2
• No episodes of ADHFc within 1 week prior to or during screening
Sample size N=6263 N=5988
Study duration 27 months 26.2 months
Primary outcome
Time to first occurrence of any component of the composite of CV
death or HF events (hHF or urgent HF visit) in the full patient
population and in patients with LVEF <60%
Time to first occurrence of any component of the composite of CV death or hHF
Secondary
outcomes
• Total number of HF events (first and recurrent) and CV deaths in the
full patient population and in patients with LVEF <60%
• Change from baseline in KCCQ-TSS at 8 months
• Time to occurrence of CV death
• Time to occurrence of death from any cause
• Occurrence of first and recurrent hHF
• eGFRb slope of change from baseline
• Time to first occurrence of sustained eGFR reduction, chronic dialysis, or
renal transplant
• Time to first hHF
• Time to CV death
• Time to all-cause mortality
• Time to diabetes onset
• Change from baseline in KCCQ at 52 weeks
• Occurrence of all-cause hospitalization
Background
therapy
• SoC treatment • SoC treatment
Completion March 2022 (estimated) April 2021 (actual)
Study Population

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Presentación del ESC Congress 2022
https://doi.org/10.1016/S0140-6736(22)01429-5
Pre-specified meta-analysis
of DELIVER and EMPEROR-Preserved
Background Study Population Results
DELIVER and EMPEROR-Preserved Population (N=12.251)
Prespecified prior tu unblinding of DELIVER
Individual participating-level data from DELIVER used to harmonize endpoint definitions and subgroups
20%
12%

8. Martina Amiguet Comins
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Presentación del ESC Congress 2022
https://doi.org/10.1016/S0140-6736(22)01429-5
Pre-specified meta-analysis
of DELIVER and EMPEROR-Preserved
Background Study Population Results
DELIVER and EMPEROR-Preserved Population (N=12.251)
Prespecified prior tu unblinding of DELIVER
Individual participating-level data from DELIVER used to harmonize endpoint definitions and subgroups
SGLT2i showed consistent benefit for all subgroups, including higher LVEF

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Presentación del ESC Congress 2022
https://doi.org/10.1016/S0140-6736(22)01429-5
Pre-specified meta-analysis
of DELIVER and EMPEROR-Preserved
23% NNT= 25
TOTALITY OF EVIDENCE OF SGLT2i in HF (N=21.947)
DAPA-HF, SOLOIST-WHF, EMPEROR-reduced, EMPEROR-preserved, DELIVER

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Presentación del ESC Congress 2022
https://doi.org/10.1016/S0140-6736(22)01429-5
Pre-specified meta-analysis
of DELIVER and EMPEROR-Preserved
Background Study Population Results Conclusions
This meta-analysis of 2 large dedicated outcomes trials of SGLT2i in HF confirms that
dapagliflozin and empagliflozin robustly reduce CV death and HF hospitalizations
“iSGLT2 deben formar parte del SOC en Insuficiencia Cardíaca, independientemente de la FEVI, el escenario o el fenotipo del
paciente ”
This results are consistent through the respecified subgroups, including LVEF>60%

11. Martina Amiguet Comins
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Presentación del ESC Congress 2022
https://doi.org/10.1016/S0140-6736(22)01429-5
Pre-specified meta-analysis
of DELIVER and EMPEROR-Preserved
Background Study Population Results Conclusions
Dr Frank Ruschitzka
discussion