Efficacy and Safety of Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction According to Age: The DELIVER Trial

Alexander Peikert; Felipe A. Martinez; Muthiah Vaduganathan; Brian L. Claggett; Ian J. Kulac; Akshay S. Desai; Pardeep S. Jhund; Rudolf A. De Boer; David Demets; Adrian F. Hernandez; Silvio E. Inzucchi; Mikhail N. Kosiborod; Carolyn S.P. Lam; Sanjiv J. Shah; Tsvetana Katova; Béla Merkely; Orly Vardeny; Ulrica Wilderäng; Daniel Lindholm; Magnus Petersson; Anna Maria Langkilde; John J.V. McMurray; Scott D. Solomon

doi:10.1161/CIRCHEARTFAILURE.122.010080

Efficacy and Safety of Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction According to Age: The DELIVER Trial

Alexander Peikert, Felipe A. Martinez, Muthiah Vaduganathan, Brian L. Claggett, Ian J. Kulac, Akshay S. Desai, Pardeep S. Jhund, Rudolf A. De Boer, David Demets, Adrian F. Hernandez, Silvio E. Inzucchi, Mikhail N. Kosiborod, Carolyn S.P. Lam, Sanjiv J. Shah, Tsvetana Katova, Béla Merkely, Orly Vardeny, Ulrica Wilderäng, Daniel Lindholm, Magnus PeterssonAnna Maria Langkilde, John J.V. McMurray, Scott D. Solomon

Medicine - Veteran's Administration Medical Center

Research output: Contribution to journal › Article › peer-review

75 Scopus citations

Abstract

BACKGROUND: The prevalence of heart failure with mildly reduced or preserved ejection fraction markedly increases with age, with older individuals disproportionately facing excess risk for mortality and hospitalization.

METHODS: The DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) randomized patients with New York Heart Association functional class II-IV and left ventricular ejection fraction >40% to either dapagliflozin or placebo for a median follow-up period of 2.3 years. We examined efficacy and safety outcomes by age categories (<55, 55-64, 65-74, and ≥75 years) and across age as a continuous measure.

RESULTS: Among 6263 randomized patients (aged 40-99 years, mean age 71.7±9.6 years), 338 (5.4%) were <55 years, 1007 (16.1%) were 55-64 years, 2326 (37.1%) were 65 to 74 years, and 2592 (41.4%) were ≥75 years. Dapagliflozin reduced the risk of the primary composite outcome compared with placebo in all age categories ( P interaction=0.95) and across the age spectrum as a continuous function ( P interaction=0.76). Similar benefits were observed for the components of the primary outcome, with no significant interaction between randomized treatment and age category. Adverse events occurred more frequently with increasing age, but there were no significant differences in predefined safety outcomes between patients randomized to dapagliflozin and placebo across all age categories.

CONCLUSIONS: In patients with heart failure and mildly reduced or preserved ejection fraction enrolled in DELIVER, dapagliflozin reduced the combined risk of cardiovascular death or worsening heart failure events across the spectrum of age, with a consistent safety profile, including among the traditionally under-treated older segment of patients ≥75 years.

REGISTRATION: URL: https://www.

CLINICALTRIALS: gov; Unique identifier: NCT03619213.

Original language	English (US)
Pages (from-to)	E010080
Journal	Circulation: Heart Failure
Volume	15
Issue number	10
DOIs	https://doi.org/10.1161/CIRCHEARTFAILURE.122.010080
State	Published - Oct 1 2022

Bibliographical note

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© 2022 Lippincott Williams and Wilkins. All rights reserved.

Keywords

aging
dapagliflozin
heart failure with mildly reduced ejection fraction
heart failure with preserved ejection fraction
SGLT2 inhibitors
Ventricular Function, Left
Humans
Middle Aged
Stroke Volume
Heart Failure/diagnosis
Aged, 80 and over
Glucosides/adverse effects
Aged

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Randomized Controlled Trial
Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1161/CIRCHEARTFAILURE.122.010080

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Peikert, A., Martinez, F. A., Vaduganathan, M., Claggett, B. L., Kulac, I. J., Desai, A. S., Jhund, P. S., De Boer, R. A., Demets, D., Hernandez, A. F., Inzucchi, S. E., Kosiborod, M. N., Lam, C. S. P., Shah, S. J., Katova, T., Merkely, B., Vardeny, O., Wilderäng, U., Lindholm, D., ... Solomon, S. D. (2022). Efficacy and Safety of Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction According to Age: The DELIVER Trial. Circulation: Heart Failure, 15(10), E010080. https://doi.org/10.1161/CIRCHEARTFAILURE.122.010080

Peikert, A, Martinez, FA, Vaduganathan, M, Claggett, BL, Kulac, IJ, Desai, AS, Jhund, PS, De Boer, RA, Demets, D, Hernandez, AF, Inzucchi, SE, Kosiborod, MN, Lam, CSP, Shah, SJ, Katova, T, Merkely, B, Vardeny, O, Wilderäng, U, Lindholm, D, Petersson, M, Langkilde, AM, McMurray, JJV & Solomon, SD 2022, 'Efficacy and Safety of Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction According to Age: The DELIVER Trial', Circulation: Heart Failure, vol. 15, no. 10, pp. E010080. https://doi.org/10.1161/CIRCHEARTFAILURE.122.010080

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title = "Efficacy and Safety of Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction According to Age: The DELIVER Trial",

abstract = "BACKGROUND: The prevalence of heart failure with mildly reduced or preserved ejection fraction markedly increases with age, with older individuals disproportionately facing excess risk for mortality and hospitalization.METHODS: The DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) randomized patients with New York Heart Association functional class II-IV and left ventricular ejection fraction >40% to either dapagliflozin or placebo for a median follow-up period of 2.3 years. We examined efficacy and safety outcomes by age categories (<55, 55-64, 65-74, and ≥75 years) and across age as a continuous measure.RESULTS: Among 6263 randomized patients (aged 40-99 years, mean age 71.7±9.6 years), 338 (5.4%) were <55 years, 1007 (16.1%) were 55-64 years, 2326 (37.1%) were 65 to 74 years, and 2592 (41.4%) were ≥75 years. Dapagliflozin reduced the risk of the primary composite outcome compared with placebo in all age categories ( P interaction=0.95) and across the age spectrum as a continuous function ( P interaction=0.76). Similar benefits were observed for the components of the primary outcome, with no significant interaction between randomized treatment and age category. Adverse events occurred more frequently with increasing age, but there were no significant differences in predefined safety outcomes between patients randomized to dapagliflozin and placebo across all age categories. CONCLUSIONS: In patients with heart failure and mildly reduced or preserved ejection fraction enrolled in DELIVER, dapagliflozin reduced the combined risk of cardiovascular death or worsening heart failure events across the spectrum of age, with a consistent safety profile, including among the traditionally under-treated older segment of patients ≥75 years.REGISTRATION: URL: https://www.CLINICALTRIALS: gov; Unique identifier: NCT03619213.",

keywords = "aging, dapagliflozin, heart failure with mildly reduced ejection fraction, heart failure with preserved ejection fraction, SGLT2 inhibitors, Ventricular Function, Left, Humans, Middle Aged, Stroke Volume, Heart Failure/diagnosis, Aged, 80 and over, Glucosides/adverse effects, Aged",

author = "Alexander Peikert and Martinez, {Felipe A.} and Muthiah Vaduganathan and Claggett, {Brian L.} and Kulac, {Ian J.} and Desai, {Akshay S.} and Jhund, {Pardeep S.} and {De Boer}, {Rudolf A.} and David Demets and Hernandez, {Adrian F.} and Inzucchi, {Silvio E.} and Kosiborod, {Mikhail N.} and Lam, {Carolyn S.P.} and Shah, {Sanjiv J.} and Tsvetana Katova and B{\'e}la Merkely and Orly Vardeny and Ulrica Wilder{\"a}ng and Daniel Lindholm and Magnus Petersson and Langkilde, {Anna Maria} and McMurray, {John J.V.} and Solomon, {Scott D.}",

year = "2022",

month = oct,

day = "1",

doi = "10.1161/CIRCHEARTFAILURE.122.010080",

language = "English (US)",

volume = "15",

pages = "E010080",

journal = "Circulation: Heart Failure",

issn = "1941-3289",

publisher = "Lippincott Williams and Wilkins",

number = "10",

}

TY - JOUR

T1 - Efficacy and Safety of Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction According to Age

T2 - The DELIVER Trial

AU - Peikert, Alexander

AU - Martinez, Felipe A.

AU - Vaduganathan, Muthiah

AU - Claggett, Brian L.

AU - Kulac, Ian J.

AU - Desai, Akshay S.

AU - Jhund, Pardeep S.

AU - De Boer, Rudolf A.

AU - Demets, David

AU - Hernandez, Adrian F.

AU - Inzucchi, Silvio E.

AU - Kosiborod, Mikhail N.

AU - Lam, Carolyn S.P.

AU - Shah, Sanjiv J.

AU - Katova, Tsvetana

AU - Merkely, Béla

AU - Vardeny, Orly

AU - Wilderäng, Ulrica

AU - Lindholm, Daniel

AU - Petersson, Magnus

AU - Langkilde, Anna Maria

AU - McMurray, John J.V.

AU - Solomon, Scott D.

PY - 2022/10/1

Y1 - 2022/10/1

N2 - BACKGROUND: The prevalence of heart failure with mildly reduced or preserved ejection fraction markedly increases with age, with older individuals disproportionately facing excess risk for mortality and hospitalization.METHODS: The DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) randomized patients with New York Heart Association functional class II-IV and left ventricular ejection fraction >40% to either dapagliflozin or placebo for a median follow-up period of 2.3 years. We examined efficacy and safety outcomes by age categories (<55, 55-64, 65-74, and ≥75 years) and across age as a continuous measure.RESULTS: Among 6263 randomized patients (aged 40-99 years, mean age 71.7±9.6 years), 338 (5.4%) were <55 years, 1007 (16.1%) were 55-64 years, 2326 (37.1%) were 65 to 74 years, and 2592 (41.4%) were ≥75 years. Dapagliflozin reduced the risk of the primary composite outcome compared with placebo in all age categories ( P interaction=0.95) and across the age spectrum as a continuous function ( P interaction=0.76). Similar benefits were observed for the components of the primary outcome, with no significant interaction between randomized treatment and age category. Adverse events occurred more frequently with increasing age, but there were no significant differences in predefined safety outcomes between patients randomized to dapagliflozin and placebo across all age categories. CONCLUSIONS: In patients with heart failure and mildly reduced or preserved ejection fraction enrolled in DELIVER, dapagliflozin reduced the combined risk of cardiovascular death or worsening heart failure events across the spectrum of age, with a consistent safety profile, including among the traditionally under-treated older segment of patients ≥75 years.REGISTRATION: URL: https://www.CLINICALTRIALS: gov; Unique identifier: NCT03619213.

AB - BACKGROUND: The prevalence of heart failure with mildly reduced or preserved ejection fraction markedly increases with age, with older individuals disproportionately facing excess risk for mortality and hospitalization.METHODS: The DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) randomized patients with New York Heart Association functional class II-IV and left ventricular ejection fraction >40% to either dapagliflozin or placebo for a median follow-up period of 2.3 years. We examined efficacy and safety outcomes by age categories (<55, 55-64, 65-74, and ≥75 years) and across age as a continuous measure.RESULTS: Among 6263 randomized patients (aged 40-99 years, mean age 71.7±9.6 years), 338 (5.4%) were <55 years, 1007 (16.1%) were 55-64 years, 2326 (37.1%) were 65 to 74 years, and 2592 (41.4%) were ≥75 years. Dapagliflozin reduced the risk of the primary composite outcome compared with placebo in all age categories ( P interaction=0.95) and across the age spectrum as a continuous function ( P interaction=0.76). Similar benefits were observed for the components of the primary outcome, with no significant interaction between randomized treatment and age category. Adverse events occurred more frequently with increasing age, but there were no significant differences in predefined safety outcomes between patients randomized to dapagliflozin and placebo across all age categories. CONCLUSIONS: In patients with heart failure and mildly reduced or preserved ejection fraction enrolled in DELIVER, dapagliflozin reduced the combined risk of cardiovascular death or worsening heart failure events across the spectrum of age, with a consistent safety profile, including among the traditionally under-treated older segment of patients ≥75 years.REGISTRATION: URL: https://www.CLINICALTRIALS: gov; Unique identifier: NCT03619213.

KW - aging

KW - dapagliflozin

KW - heart failure with mildly reduced ejection fraction

KW - heart failure with preserved ejection fraction

KW - SGLT2 inhibitors

KW - Ventricular Function, Left

KW - Humans

KW - Middle Aged

KW - Stroke Volume

KW - Heart Failure/diagnosis

KW - Aged, 80 and over

KW - Glucosides/adverse effects

KW - Aged

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U2 - 10.1161/CIRCHEARTFAILURE.122.010080

DO - 10.1161/CIRCHEARTFAILURE.122.010080

M3 - Article

C2 - 36029467

AN - SCOPUS:85138681204

SN - 1941-3289

VL - 15

SP - E010080

JO - Circulation: Heart Failure

JF - Circulation: Heart Failure

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ER -

Efficacy and Safety of Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction According to Age: The DELIVER Trial

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

Publisher link

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