Heart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fraction: Insights from DELIVER

Jawad H. Butt; Henri Lu; Toru Kondo; Erasmus Bachus; Rudolf A. de Boer; Silvio E. Inzucchi; Pardeep S. Jhund; Mikhail N. Kosiborod; Carolyn S.P. Lam; Felipe A. Martinez; Muthiah Vaduganathan; Scott D. Solomon; John J.V. McMurray

doi:10.1002/ejhf.3000

Heart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fraction: Insights from DELIVER

Jawad H. Butt, Henri Lu, Toru Kondo, Erasmus Bachus, Rudolf A. de Boer, Silvio E. Inzucchi, Pardeep S. Jhund, Mikhail N. Kosiborod, Carolyn S.P. Lam, Felipe A. Martinez, Muthiah Vaduganathan, Scott D. Solomon, John J.V. McMurray^*

^*Corresponding author for this work

Cardiology

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

13 Citations (Scopus)

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Abstract

Aim:

Chronic obstructive pulmonary disease (COPD) is common in heart failure with a mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and is associated with worse outcomes. In a pre-specified analysis of DELIVER, we investigated the relationship between COPD status and outcomes, and the efficacy and safety of dapagliflozin, compared with placebo, according to COPD status.

Methods and results:

Patients with severe pulmonary disease (including COPD) were excluded from the trial. The primary outcome was a composite of cardiovascular death or worsening heart failure. Of the 6261 patients with data on baseline COPD status, 694 (11.1%) had a known history of this condition. The risk of the primary endpoint was higher in patients with mild-to-moderate COPD compared with those without COPD (adjusted hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.08–1.51). The benefit of dapagliflozin on the primary outcome was consistent irrespective of COPD status (no COPD: HR 0.82 [95% CI 0.72–0.93]; COPD: HR 0.82 [95% CI 0.62–1.10]; p_interaction = 0.98). Consistent effects were observed for heart failure, cardiovascular, and all-cause hospitalization, and deaths, and composites of these. Dapagliflozin, as compared with placebo, improved the Kansas City Cardiomyopathy Questionnaire scores from baseline to 8 months to a similar extent in patients with and without mild-to-moderate COPD (p_interaction ≥ 0.63). Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of COPD status. '

Conclusions:

Mild-to-moderate COPD is common in patients with HFmrEF/HFpEF and is associated with worse outcomes. The beneficial effects of dapagliflozin compared with placebo on clinical events and symptoms were consistent, regardless of COPD status. Clinical Trial Registration: ClinicalTrials.gov NCT03619213.

Original language	English
Pages (from-to)	2078-2090
Number of pages	13
Journal	European Journal of Heart Failure
Volume	25
Issue number	11
Early online date	26 Aug 2023
DOIs	https://doi.org/10.1002/ejhf.3000
Publication status	Published - Nov 2023

Bibliographical note

Funding Information:
The DELIVER trial was funded by AstraZeneca. Profs. McMurray and Jhund are supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217 and the Vera Melrose Heart Failure Research Fund.

Publisher Copyright:
© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

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Heart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fractionFinal published version, 567 KBLicence: CC BY

Cite this

Butt, J. H., Lu, H., Kondo, T., Bachus, E., de Boer, R. A., Inzucchi, S. E., Jhund, P. S., Kosiborod, M. N., Lam, C. S. P., Martinez, F. A., Vaduganathan, M., Solomon, S. D., & McMurray, J. J. V. (2023). Heart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fraction: Insights from DELIVER. European Journal of Heart Failure, 25(11), 2078-2090. https://doi.org/10.1002/ejhf.3000

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title = "Heart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fraction: Insights from DELIVER",

abstract = "Aim: Chronic obstructive pulmonary disease (COPD) is common in heart failure with a mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and is associated with worse outcomes. In a pre-specified analysis of DELIVER, we investigated the relationship between COPD status and outcomes, and the efficacy and safety of dapagliflozin, compared with placebo, according to COPD status. Methods and results: Patients with severe pulmonary disease (including COPD) were excluded from the trial. The primary outcome was a composite of cardiovascular death or worsening heart failure. Of the 6261 patients with data on baseline COPD status, 694 (11.1%) had a known history of this condition. The risk of the primary endpoint was higher in patients with mild-to-moderate COPD compared with those without COPD (adjusted hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.08–1.51). The benefit of dapagliflozin on the primary outcome was consistent irrespective of COPD status (no COPD: HR 0.82 [95% CI 0.72–0.93]; COPD: HR 0.82 [95% CI 0.62–1.10]; pinteraction = 0.98). Consistent effects were observed for heart failure, cardiovascular, and all-cause hospitalization, and deaths, and composites of these. Dapagliflozin, as compared with placebo, improved the Kansas City Cardiomyopathy Questionnaire scores from baseline to 8 months to a similar extent in patients with and without mild-to-moderate COPD (pinteraction ≥ 0.63). Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of COPD status. 'Conclusions: Mild-to-moderate COPD is common in patients with HFmrEF/HFpEF and is associated with worse outcomes. The beneficial effects of dapagliflozin compared with placebo on clinical events and symptoms were consistent, regardless of COPD status. Clinical Trial Registration: ClinicalTrials.gov NCT03619213.",

author = "Butt, {Jawad H.} and Henri Lu and Toru Kondo and Erasmus Bachus and {de Boer}, {Rudolf A.} and Inzucchi, {Silvio E.} and Jhund, {Pardeep S.} and Kosiborod, {Mikhail N.} and Lam, {Carolyn S.P.} and Martinez, {Felipe A.} and Muthiah Vaduganathan and Solomon, {Scott D.} and McMurray, {John J.V.}",

note = "Funding Information: The DELIVER trial was funded by AstraZeneca. Profs. McMurray and Jhund are supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217 and the Vera Melrose Heart Failure Research Fund. Publisher Copyright: {\textcopyright} 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.",

year = "2023",

month = nov,

doi = "10.1002/ejhf.3000",

language = "English",

volume = "25",

pages = "2078--2090",

journal = "European Journal of Heart Failure",

issn = "1388-9842",

publisher = "John Wiley & Sons Ltd.",

number = "11",

}

Butt, JH, Lu, H, Kondo, T, Bachus, E, de Boer, RA, Inzucchi, SE, Jhund, PS, Kosiborod, MN, Lam, CSP, Martinez, FA, Vaduganathan, M, Solomon, SD & McMurray, JJV 2023, 'Heart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fraction: Insights from DELIVER', European Journal of Heart Failure, vol. 25, no. 11, pp. 2078-2090. https://doi.org/10.1002/ejhf.3000

Heart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fraction: Insights from DELIVER. / Butt, Jawad H.; Lu, Henri; Kondo, Toru et al.
In: European Journal of Heart Failure, Vol. 25, No. 11, 11.2023, p. 2078-2090.

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

TY - JOUR

T1 - Heart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fraction

T2 - Insights from DELIVER

AU - Butt, Jawad H.

AU - Lu, Henri

AU - Kondo, Toru

AU - Bachus, Erasmus

AU - de Boer, Rudolf A.

AU - Inzucchi, Silvio E.

AU - Jhund, Pardeep S.

AU - Kosiborod, Mikhail N.

AU - Lam, Carolyn S.P.

AU - Martinez, Felipe A.

AU - Vaduganathan, Muthiah

AU - Solomon, Scott D.

AU - McMurray, John J.V.

N1 - Funding Information: The DELIVER trial was funded by AstraZeneca. Profs. McMurray and Jhund are supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217 and the Vera Melrose Heart Failure Research Fund. Publisher Copyright: © 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

PY - 2023/11

Y1 - 2023/11

N2 - Aim: Chronic obstructive pulmonary disease (COPD) is common in heart failure with a mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and is associated with worse outcomes. In a pre-specified analysis of DELIVER, we investigated the relationship between COPD status and outcomes, and the efficacy and safety of dapagliflozin, compared with placebo, according to COPD status. Methods and results: Patients with severe pulmonary disease (including COPD) were excluded from the trial. The primary outcome was a composite of cardiovascular death or worsening heart failure. Of the 6261 patients with data on baseline COPD status, 694 (11.1%) had a known history of this condition. The risk of the primary endpoint was higher in patients with mild-to-moderate COPD compared with those without COPD (adjusted hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.08–1.51). The benefit of dapagliflozin on the primary outcome was consistent irrespective of COPD status (no COPD: HR 0.82 [95% CI 0.72–0.93]; COPD: HR 0.82 [95% CI 0.62–1.10]; pinteraction = 0.98). Consistent effects were observed for heart failure, cardiovascular, and all-cause hospitalization, and deaths, and composites of these. Dapagliflozin, as compared with placebo, improved the Kansas City Cardiomyopathy Questionnaire scores from baseline to 8 months to a similar extent in patients with and without mild-to-moderate COPD (pinteraction ≥ 0.63). Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of COPD status. 'Conclusions: Mild-to-moderate COPD is common in patients with HFmrEF/HFpEF and is associated with worse outcomes. The beneficial effects of dapagliflozin compared with placebo on clinical events and symptoms were consistent, regardless of COPD status. Clinical Trial Registration: ClinicalTrials.gov NCT03619213.

AB - Aim: Chronic obstructive pulmonary disease (COPD) is common in heart failure with a mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and is associated with worse outcomes. In a pre-specified analysis of DELIVER, we investigated the relationship between COPD status and outcomes, and the efficacy and safety of dapagliflozin, compared with placebo, according to COPD status. Methods and results: Patients with severe pulmonary disease (including COPD) were excluded from the trial. The primary outcome was a composite of cardiovascular death or worsening heart failure. Of the 6261 patients with data on baseline COPD status, 694 (11.1%) had a known history of this condition. The risk of the primary endpoint was higher in patients with mild-to-moderate COPD compared with those without COPD (adjusted hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.08–1.51). The benefit of dapagliflozin on the primary outcome was consistent irrespective of COPD status (no COPD: HR 0.82 [95% CI 0.72–0.93]; COPD: HR 0.82 [95% CI 0.62–1.10]; pinteraction = 0.98). Consistent effects were observed for heart failure, cardiovascular, and all-cause hospitalization, and deaths, and composites of these. Dapagliflozin, as compared with placebo, improved the Kansas City Cardiomyopathy Questionnaire scores from baseline to 8 months to a similar extent in patients with and without mild-to-moderate COPD (pinteraction ≥ 0.63). Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of COPD status. 'Conclusions: Mild-to-moderate COPD is common in patients with HFmrEF/HFpEF and is associated with worse outcomes. The beneficial effects of dapagliflozin compared with placebo on clinical events and symptoms were consistent, regardless of COPD status. Clinical Trial Registration: ClinicalTrials.gov NCT03619213.

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U2 - 10.1002/ejhf.3000

DO - 10.1002/ejhf.3000

M3 - Article

C2 - 37634087

AN - SCOPUS:85169422300

SN - 1388-9842

VL - 25

SP - 2078

EP - 2090

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

IS - 11

ER -

Heart failure, chronic obstructive pulmonary disease and efficacy and safety of dapagliflozin in heart failure with mildly reduced or preserved ejection fraction: Insights from DELIVER

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