Dapagliflozin and Timing of Prior Heart Failure Hospitalization: A Patient-Level Meta-Analysis of DAPA-HF and DELIVER

Jawad H Butt; Pardeep S Jhund; Kieran F Docherty; Brian L Claggett; Muthiah Vaduganathan; Erasmus Bachus; Adrian F Hernandez; Carolyn S P Lam; Silvio E Inzucchi; Felipe A Martinez; Rudolf A de Boer; Mikhail N Kosiborod; Akshay S Desai; Lars Køber; Piotr Ponikowski; Marc S Sabatine; Scott D Solomon; John J V McMurray

doi:10.1016/j.jchf.2024.01.018

Dapagliflozin and Timing of Prior Heart Failure Hospitalization: A Patient-Level Meta-Analysis of DAPA-HF and DELIVER

Jawad H Butt, Pardeep S Jhund, Kieran F Docherty, Brian L Claggett, Muthiah Vaduganathan, Erasmus Bachus, Adrian F Hernandez, Carolyn S P Lam, Silvio E Inzucchi, Felipe A Martinez, Rudolf A de Boer, Mikhail N Kosiborod, Akshay S Desai, Lars Køber, Piotr Ponikowski, Marc S Sabatine, Scott D Solomon, John J V McMurray^*

^*Corresponding author af dette arbejde

Afdeling for Hjertesygdomme

2 Citationer (Scopus)

Abstract

BACKGROUND: Patients recently hospitalized for heart failure (HF) are at a higher risk of adverse clinical outcomes, but they may experience a greater absolute and relative benefit from effective therapies than individuals who are considered more "stable."

OBJECTIVES: The authors examined the effects of dapagliflozin according to the timing of prior HF hospitalization in a patient-level pooled analysis of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure).

METHODS: A total of 11,007 patients were randomized in DAPA-HF and DELIVER. The primary outcome was the composite of worsening HF or cardiovascular death.

RESULTS: In total, 12.4% were hospitalized for HF within 3 months of randomization, 14.2% between 3 and 12 months, and 16.8% more than 1 year before randomization, whereas 56.5% had not been hospitalized. The risk of the primary endpoint was inversely associated with time from prior HF hospitalization, and patients with a recent HF hospitalization had the highest risk. Compared with placebo, dapagliflozin reduced the risk of the primary outcome across HF hospitalization category (0-3 months, HR: 0.66 [95% CI: 0.55-0.81]; 3-12 months, HR: 0.73 [95% CI: 0.59-0.90]; >1 year, HR: 0.91 [95% CI: 0.74-1.12]; and no prior hospitalization, HR: 0.83 [95% CI: 0.73-0.94]; Pinteraction = 0.09). The number of patients needed to treat with dapagliflozin to prevent 1 event over the median follow-up of 22 months was 13, 20, 23, and 28, respectively. The beneficial effect was consistent across the range of LVEF regardless of HF hospitalization category.

CONCLUSIONS: The relative benefits of dapagliflozin were consistent across the range of LVEF regardless of the timing of the most recent HF hospitalization with a greater absolute benefit in patients with recent hospitalization.

Originalsprog	Engelsk
Tidsskrift	JACC. Heart failure
Vol/bind	12
Udgave nummer	9
Sider (fra-til)	1586-1599
Antal sider	14
ISSN	2213-1779
DOI	https://doi.org/10.1016/j.jchf.2024.01.018
Status	Udgivet - sep. 2024

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10.1016/j.jchf.2024.01.018

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Butt, J. H., Jhund, P. S., Docherty, K. F., Claggett, B. L., Vaduganathan, M., Bachus, E., Hernandez, A. F., Lam, C. S. P., Inzucchi, S. E., Martinez, F. A., de Boer, R. A., Kosiborod, M. N., Desai, A. S., Køber, L., Ponikowski, P., Sabatine, M. S., Solomon, S. D., & McMurray, J. J. V. (2024). Dapagliflozin and Timing of Prior Heart Failure Hospitalization: A Patient-Level Meta-Analysis of DAPA-HF and DELIVER. JACC. Heart failure, 12(9), 1586-1599. https://doi.org/10.1016/j.jchf.2024.01.018

Butt, JH, Jhund, PS, Docherty, KF, Claggett, BL, Vaduganathan, M, Bachus, E, Hernandez, AF, Lam, CSP, Inzucchi, SE, Martinez, FA, de Boer, RA, Kosiborod, MN, Desai, AS, Køber, L, Ponikowski, P, Sabatine, MS, Solomon, SD & McMurray, JJV 2024, 'Dapagliflozin and Timing of Prior Heart Failure Hospitalization: A Patient-Level Meta-Analysis of DAPA-HF and DELIVER', JACC. Heart failure, bind 12, nr. 9, s. 1586-1599. https://doi.org/10.1016/j.jchf.2024.01.018

@article{569488cb1e7349f6b7b5c42b2638007a,

title = "Dapagliflozin and Timing of Prior Heart Failure Hospitalization: A Patient-Level Meta-Analysis of DAPA-HF and DELIVER",

abstract = "BACKGROUND: Patients recently hospitalized for heart failure (HF) are at a higher risk of adverse clinical outcomes, but they may experience a greater absolute and relative benefit from effective therapies than individuals who are considered more {"}stable.{"}OBJECTIVES: The authors examined the effects of dapagliflozin according to the timing of prior HF hospitalization in a patient-level pooled analysis of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure).METHODS: A total of 11,007 patients were randomized in DAPA-HF and DELIVER. The primary outcome was the composite of worsening HF or cardiovascular death.RESULTS: In total, 12.4% were hospitalized for HF within 3 months of randomization, 14.2% between 3 and 12 months, and 16.8% more than 1 year before randomization, whereas 56.5% had not been hospitalized. The risk of the primary endpoint was inversely associated with time from prior HF hospitalization, and patients with a recent HF hospitalization had the highest risk. Compared with placebo, dapagliflozin reduced the risk of the primary outcome across HF hospitalization category (0-3 months, HR: 0.66 [95% CI: 0.55-0.81]; 3-12 months, HR: 0.73 [95% CI: 0.59-0.90]; >1 year, HR: 0.91 [95% CI: 0.74-1.12]; and no prior hospitalization, HR: 0.83 [95% CI: 0.73-0.94]; Pinteraction = 0.09). The number of patients needed to treat with dapagliflozin to prevent 1 event over the median follow-up of 22 months was 13, 20, 23, and 28, respectively. The beneficial effect was consistent across the range of LVEF regardless of HF hospitalization category.CONCLUSIONS: The relative benefits of dapagliflozin were consistent across the range of LVEF regardless of the timing of the most recent HF hospitalization with a greater absolute benefit in patients with recent hospitalization.",

keywords = "clinical trial, heart failure, outcomes, Humans, Middle Aged, Male, Stroke Volume/physiology, Benzhydryl Compounds/therapeutic use, Sodium-Glucose Transporter 2 Inhibitors/therapeutic use, Randomized Controlled Trials as Topic, Heart Failure/drug therapy, Time Factors, Female, Hospitalization/statistics & numerical data, Aged, Glucosides/therapeutic use",

author = "Butt, {Jawad H} and Jhund, {Pardeep S} and Docherty, {Kieran F} and Claggett, {Brian L} and Muthiah Vaduganathan and Erasmus Bachus and Hernandez, {Adrian F} and Lam, {Carolyn S P} and Inzucchi, {Silvio E} and Martinez, {Felipe A} and {de Boer}, {Rudolf A} and Kosiborod, {Mikhail N} and Desai, {Akshay S} and Lars K{\o}ber and Piotr Ponikowski and Sabatine, {Marc S} and Solomon, {Scott D} and McMurray, {John J V}",

year = "2024",

month = sep,

doi = "10.1016/j.jchf.2024.01.018",

language = "English",

volume = "12",

pages = "1586--1599",

journal = "JACC. Heart failure",

issn = "2213-1779",

publisher = "Elsevier BV",

number = "9",

}

TY - JOUR

T1 - Dapagliflozin and Timing of Prior Heart Failure Hospitalization

T2 - A Patient-Level Meta-Analysis of DAPA-HF and DELIVER

AU - Butt, Jawad H

AU - Jhund, Pardeep S

AU - Docherty, Kieran F

AU - Claggett, Brian L

AU - Vaduganathan, Muthiah

AU - Bachus, Erasmus

AU - Hernandez, Adrian F

AU - Lam, Carolyn S P

AU - Inzucchi, Silvio E

AU - Martinez, Felipe A

AU - de Boer, Rudolf A

AU - Kosiborod, Mikhail N

AU - Desai, Akshay S

AU - Køber, Lars

AU - Ponikowski, Piotr

AU - Sabatine, Marc S

AU - Solomon, Scott D

AU - McMurray, John J V

PY - 2024/9

Y1 - 2024/9

N2 - BACKGROUND: Patients recently hospitalized for heart failure (HF) are at a higher risk of adverse clinical outcomes, but they may experience a greater absolute and relative benefit from effective therapies than individuals who are considered more "stable."OBJECTIVES: The authors examined the effects of dapagliflozin according to the timing of prior HF hospitalization in a patient-level pooled analysis of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure).METHODS: A total of 11,007 patients were randomized in DAPA-HF and DELIVER. The primary outcome was the composite of worsening HF or cardiovascular death.RESULTS: In total, 12.4% were hospitalized for HF within 3 months of randomization, 14.2% between 3 and 12 months, and 16.8% more than 1 year before randomization, whereas 56.5% had not been hospitalized. The risk of the primary endpoint was inversely associated with time from prior HF hospitalization, and patients with a recent HF hospitalization had the highest risk. Compared with placebo, dapagliflozin reduced the risk of the primary outcome across HF hospitalization category (0-3 months, HR: 0.66 [95% CI: 0.55-0.81]; 3-12 months, HR: 0.73 [95% CI: 0.59-0.90]; >1 year, HR: 0.91 [95% CI: 0.74-1.12]; and no prior hospitalization, HR: 0.83 [95% CI: 0.73-0.94]; Pinteraction = 0.09). The number of patients needed to treat with dapagliflozin to prevent 1 event over the median follow-up of 22 months was 13, 20, 23, and 28, respectively. The beneficial effect was consistent across the range of LVEF regardless of HF hospitalization category.CONCLUSIONS: The relative benefits of dapagliflozin were consistent across the range of LVEF regardless of the timing of the most recent HF hospitalization with a greater absolute benefit in patients with recent hospitalization.

AB - BACKGROUND: Patients recently hospitalized for heart failure (HF) are at a higher risk of adverse clinical outcomes, but they may experience a greater absolute and relative benefit from effective therapies than individuals who are considered more "stable."OBJECTIVES: The authors examined the effects of dapagliflozin according to the timing of prior HF hospitalization in a patient-level pooled analysis of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure).METHODS: A total of 11,007 patients were randomized in DAPA-HF and DELIVER. The primary outcome was the composite of worsening HF or cardiovascular death.RESULTS: In total, 12.4% were hospitalized for HF within 3 months of randomization, 14.2% between 3 and 12 months, and 16.8% more than 1 year before randomization, whereas 56.5% had not been hospitalized. The risk of the primary endpoint was inversely associated with time from prior HF hospitalization, and patients with a recent HF hospitalization had the highest risk. Compared with placebo, dapagliflozin reduced the risk of the primary outcome across HF hospitalization category (0-3 months, HR: 0.66 [95% CI: 0.55-0.81]; 3-12 months, HR: 0.73 [95% CI: 0.59-0.90]; >1 year, HR: 0.91 [95% CI: 0.74-1.12]; and no prior hospitalization, HR: 0.83 [95% CI: 0.73-0.94]; Pinteraction = 0.09). The number of patients needed to treat with dapagliflozin to prevent 1 event over the median follow-up of 22 months was 13, 20, 23, and 28, respectively. The beneficial effect was consistent across the range of LVEF regardless of HF hospitalization category.CONCLUSIONS: The relative benefits of dapagliflozin were consistent across the range of LVEF regardless of the timing of the most recent HF hospitalization with a greater absolute benefit in patients with recent hospitalization.

KW - clinical trial

KW - heart failure

KW - outcomes

KW - Humans

KW - Middle Aged

KW - Male

KW - Stroke Volume/physiology

KW - Benzhydryl Compounds/therapeutic use

KW - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use

KW - Randomized Controlled Trials as Topic

KW - Heart Failure/drug therapy

KW - Time Factors

KW - Female

KW - Hospitalization/statistics & numerical data

KW - Aged

KW - Glucosides/therapeutic use

UR - http://www.scopus.com/inward/record.url?scp=85193941920&partnerID=8YFLogxK

U2 - 10.1016/j.jchf.2024.01.018

DO - 10.1016/j.jchf.2024.01.018

M3 - Journal article

C2 - 38573262

SN - 2213-1779

VL - 12

SP - 1586

EP - 1599

JO - JACC. Heart failure

JF - JACC. Heart failure

IS - 9

ER -

Dapagliflozin and Timing of Prior Heart Failure Hospitalization: A Patient-Level Meta-Analysis of DAPA-HF and DELIVER

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