The document summarizes the DELIVER trial which studied the effects of dapagliflozin in patients with heart failure with preserved ejection fraction (HFpEF) and mildly reduced ejection fraction. The trial found that dapagliflozin reduced the composite of worsening heart failure events, cardiovascular death, and total worsening heart failure events compared to placebo in over 6,000 patients. The benefits were consistent across subgroups including those with and without diabetes, prior reduced ejection fraction, and recent hospitalization for heart failure.

1. Dapagliflozin in HFpEF &
mild HFrEF
Raquel Weinberg
Journal
Club
2022
DELIVER trial, published in NEJM on
August 27, 2022
DOI: 10.1056/NEJMoa2206286

2. Table of contents
SGLT2 inhibitors
HFrEF vs HFpEF
Background
01 Methods
Study design
Subpopulations
Outcomes of interest
02
Results
03 Conclusions
04

3. Background
SGLT2 inhibitors
HFpEF vs. HFrEF
01

4. - MOA: blocks the Na+/glucose transporter in
the PCT, which → ↓ glucose absorption.
- Since approval for use in DM management,
started using in more scenarios, w/wo dx of
DM:
- HFrEF → DAPA-HF, 2019.
- CKD → DAPA-CKD, 2020 stopped early d/t
overwhelming benefit of the drug, same w/
EMPA-KIDNEY & CREDENCE.
SGLT2 inhibitors
Dapagliflozin Farxiga
Empagliflozin Jardiance
Canagliflozin Invokana
- Adverse effects:
- Dehydration → hypotension.
- Glucosuria → genitourinal fungal infex.
- Ketoacidosis → can be “euglycemic.”
- Limb amputation → controversial, particularly w/
canagliflozin.

5. (systolic) (diastolic)
Image source

6. Methods
Study design
Outcomes of interest
Subpopulations
02

7. Study design
matching placebo
3,132 pts
dapagliflozin 10 mg
3,131 pts
6,363 pts
10,418 pts
screened
➔ ≥ 40 y/o
➔ ± T2DM
➔ LVEF >40%
➔ ↑ ANP/BNP
- “Phase 3, international, multicenter,
parallel-group, event-driven.”
- Screening occurred @ 353 centers in
20 countries.
- Double-blind RCT.
- Collab w/ sponsor AstraZeneca.
- Attrition:
- Dapagliflozin was d/c in 444 pts for
reasons other than death.
- Placebo was d/c in 442 pts for reasons
other than death.
- Mean duration of f/u: 2.3 years

8. Primary outcomes of interest
Unplanned
hospitalization for HF
Urgent visit for HF Cardiovascular death
“Composite of worsening heart failure”

9. Secondary outcomes of interest
Total # of worsening
HF events
Total # of
cardiovascular deaths
Δ from baseline in
total sx score on the
KCCQ*
*KCCQ: Kansas City Cardiomyopathy Questionnaire

10. T2DM HTN
H/o HFrEF
≤40%*
Subpopulations investigated
Dapa Placebo
1,401 (44.7%) 1,405 (44.9%)
Dapa Placebo
2,755 (88%) 2,798 (89.3%)
Dapa Placebo
572 (18.3%) 579 (18.5%)
placebo
3,132 pts
dapagliflozin 10 mg
3,131 pts
Mean EF 54.3%
(±8.9)
Mean EF 54.0%
(±8.6)
*All of these pts had EF >40% by time of enrollment.

11. Results
03

13. Results interpretation
Effect of dapagliflozin on primary outcome was similar across various groups;
-In pts w/wo T2DM.
-In pts who were enrolled during or w/in 30 days after hospitalization for HF &
pts who were not enrolled during this time range.
-In pts w/wo previous HFrEF (≤40%) that had improved by the time of enrollment.
-Among pts w/wo COVID-19 diagnosis (this was censored to the investigators).
Overall results were similar when death from noncardiac causes was taken into
account as a competing risk.

14. Conclusions
04

15. ● Compared to placebo, the dapagliflozin group had:
○ Fewer total worsening HF events.
○ Lower rates of cardiovascular death.
○ Lower sx burden.
Main discussion points
● Also had broad inclusion criteria and ∴ can generalize to greater population:
○ Pts who were hospitalized or recently-hospitalized.
○ Pts w/ previous HFrEF that had improved to >40%.
○ Pts for whom evidence-based tx is limited.

16. - DAPA-HF: 2019, Dapagliflozin in Patients with Heart Failure and Reduced
Ejection Fraction.
- DELIVER shows benefit for pts w/ EF >40%.
Expansion on prior studies
- EMPEROR-Preserved: 2021, Empagliflozin Outcome Trial in Patients
with Chronic Heart Failure with Preserved Ejection Fraction.
- Similarly, pts w/ EF >40%, but w/ empagliflozin.
- Noted w/ EMPEROR that there was attenuation of benefit in the
highest range of EF, which was not seen in the DELIVER trial.

17. - Mentioned by the authors; only 5% of the patients enrolled were Black.
- Noted, however, that this was representative of particular regions
studied.
- The study design was not created to assess whether dapagliflozin directly
prevents mortality alone, ∴ additional studies will follow.
Limitations
- D/t COVID-19, the KCCQ sx burden assessment occurred before March
11, 2020. Thus, some pts did not have this data available.

18. ‫תכלס‬
Further support for the use of SGLT2i as
essential tx in pts w/ HF, regardless of:
- Presence of absence of T2DM
- Ejection fraction

19. References
DAPA-HF
DAPA-CKD
EMPEROR-Preserved
EMPA-KIDNEY
CREDENCE
UptoDate: Dapagliflozin
UptoDate: HFpEF
Harding, E., Marques, S. C., Mes, M., Murphy, M. (2020). Spotlight on HFpEF: heart failure with
preserved ejection fraction. Heart Failure Policy Network. Available here.

20. CREDITS: This presentation template was created
by Slidesgo, including icons by Flaticon and
infographics & images by Freepik
Questions?
Raquel Weinberg
raquelw@post.bgu.ac.il
WhatsApp +1 (301) 525-5229
SMS +972 (058) 696-7625

21. Appendix A
ESC 2022 Guidelines for
HFrEF

22. Appendix B
Levels of evidence/
recommendations