Contemporary Use and Implications of Beta-Blockers in Patients With HFmrEF or HFpEF: The DELIVER Trial

Alexander Peikert; Bradley A. Bart; Muthiah Vaduganathan; Brian L. Claggett; Ian J. Kulac; Mikhail N. Kosiborod; Akshay S. Desai; Pardeep S. Jhund; Carolyn S.P. Lam; Silvio E. Inzucchi; Felipe A. Martinez; Rudolf A. de Boer; Adrian F. Hernandez; Sanjiv J. Shah; Magnus Petersson; Anna Maria Langkilde; John J.V. McMurray; Scott D. Solomon; Orly Vardeny

doi:10.1016/j.jchf.2023.09.007

Contemporary Use and Implications of Beta-Blockers in Patients With HFmrEF or HFpEF: The DELIVER Trial

Alexander Peikert, Bradley A. Bart, Muthiah Vaduganathan, Brian L. Claggett, Ian J. Kulac, Mikhail N. Kosiborod, Akshay S. Desai, Pardeep S. Jhund, Carolyn S.P. Lam, Silvio E. Inzucchi, Felipe A. Martinez, Rudolf A. de Boer, Adrian F. Hernandez, Sanjiv J. Shah, Magnus Petersson, Anna Maria Langkilde, John J.V. McMurray, Scott D. Solomon, Orly Vardeny

Medicine - Veteran's Administration Medical Center

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

2 Scopus citations

Abstract

Background: Although beta-blockers are not recommended for the treatment of heart failure with preserved ejection fraction (HFpEF) according to the latest European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines, these therapies remain commonly used for comorbidity management. There has been concern that beta-blockers may adversely influence clinical outcomes by limiting chronotropic response in HFpEF. Objectives: This study sought to examine the contemporary use and implications of beta-blockers in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HFpEF. Methods: In the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial, a total of 6,263 patients with symptomatic heart failure (HF) with a left ventricular ejection fraction (LVEF) >40% were randomized to dapagliflozin or placebo across 20 countries. In this prespecified analysis, efficacy and safety outcomes were examined according to beta-blocker use at randomization. The primary outcome was cardiovascular death or worsening HF. Results: Overall, beta-blockers were used in 5,177 patients (83%), with wide variation by geographic region. Beta-blocker use was associated with a lower risk of the primary outcome in covariate-adjusted models (HR: 0.70; 95% CI: 0.60-0.83). Dapagliflozin consistently reduced the risk of the primary outcome in patients taking beta-blockers (HR: 0.82; 95% CI: 0.72-0.94) and in patients not taking beta-blockers (HR: 0.79; 95% CI: 0.61-1.03; P_interaction = 0.85), with similar findings for key secondary endpoints. Adverse events were balanced between patients randomized to dapagliflozin and placebo, regardless of background beta-blocker use. Conclusions: In patients with HFmrEF or HFpEF who were enrolled in DELIVER, 4 out of 5 participants were treated with a beta-blocker. Beta-blocker use was not associated with a higher risk of worsening HF or cardiovascular death. Dapagliflozin consistently and safely reduced clinical events, irrespective of background beta-blocker use.

Original language	English (US)
Pages (from-to)	631-644
Number of pages	14
Journal	JACC: Heart Failure
Volume	12
Issue number	4
DOIs	https://doi.org/10.1016/j.jchf.2023.09.007
State	Published - Apr 2024

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Publisher Copyright:
© 2024 The Authors

Keywords

SGLT2 inhibitors
beta-blockers
heart failure with mildly reduced ejection fraction
heart failure with preserved ejection fraction

PubMed: MeSH publication types

Randomized Controlled Trial
Journal Article

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10.1016/j.jchf.2023.09.007

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Peikert, A., Bart, B. A., Vaduganathan, M., Claggett, B. L., Kulac, I. J., Kosiborod, M. N., Desai, A. S., Jhund, P. S., Lam, C. S. P., Inzucchi, S. E., Martinez, F. A., de Boer, R. A., Hernandez, A. F., Shah, S. J., Petersson, M., Langkilde, A. M., McMurray, J. J. V., Solomon, S. D., & Vardeny, O. (2024). Contemporary Use and Implications of Beta-Blockers in Patients With HFmrEF or HFpEF: The DELIVER Trial. JACC: Heart Failure, 12(4), 631-644. https://doi.org/10.1016/j.jchf.2023.09.007

Peikert, A, Bart, BA, Vaduganathan, M, Claggett, BL, Kulac, IJ, Kosiborod, MN, Desai, AS, Jhund, PS, Lam, CSP, Inzucchi, SE, Martinez, FA, de Boer, RA, Hernandez, AF, Shah, SJ, Petersson, M, Langkilde, AM, McMurray, JJV, Solomon, SD & Vardeny, O 2024, 'Contemporary Use and Implications of Beta-Blockers in Patients With HFmrEF or HFpEF: The DELIVER Trial', JACC: Heart Failure, vol. 12, no. 4, pp. 631-644. https://doi.org/10.1016/j.jchf.2023.09.007

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title = "Contemporary Use and Implications of Beta-Blockers in Patients With HFmrEF or HFpEF: The DELIVER Trial",

abstract = "Background: Although beta-blockers are not recommended for the treatment of heart failure with preserved ejection fraction (HFpEF) according to the latest European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines, these therapies remain commonly used for comorbidity management. There has been concern that beta-blockers may adversely influence clinical outcomes by limiting chronotropic response in HFpEF. Objectives: This study sought to examine the contemporary use and implications of beta-blockers in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HFpEF. Methods: In the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial, a total of 6,263 patients with symptomatic heart failure (HF) with a left ventricular ejection fraction (LVEF) >40% were randomized to dapagliflozin or placebo across 20 countries. In this prespecified analysis, efficacy and safety outcomes were examined according to beta-blocker use at randomization. The primary outcome was cardiovascular death or worsening HF. Results: Overall, beta-blockers were used in 5,177 patients (83%), with wide variation by geographic region. Beta-blocker use was associated with a lower risk of the primary outcome in covariate-adjusted models (HR: 0.70; 95% CI: 0.60-0.83). Dapagliflozin consistently reduced the risk of the primary outcome in patients taking beta-blockers (HR: 0.82; 95% CI: 0.72-0.94) and in patients not taking beta-blockers (HR: 0.79; 95% CI: 0.61-1.03; Pinteraction = 0.85), with similar findings for key secondary endpoints. Adverse events were balanced between patients randomized to dapagliflozin and placebo, regardless of background beta-blocker use. Conclusions: In patients with HFmrEF or HFpEF who were enrolled in DELIVER, 4 out of 5 participants were treated with a beta-blocker. Beta-blocker use was not associated with a higher risk of worsening HF or cardiovascular death. Dapagliflozin consistently and safely reduced clinical events, irrespective of background beta-blocker use.",

keywords = "SGLT2 inhibitors, beta-blockers, heart failure with mildly reduced ejection fraction, heart failure with preserved ejection fraction",

author = "Alexander Peikert and Bart, {Bradley A.} and Muthiah Vaduganathan and Claggett, {Brian L.} and Kulac, {Ian J.} and Kosiborod, {Mikhail N.} and Desai, {Akshay S.} and Jhund, {Pardeep S.} and Lam, {Carolyn S.P.} and Inzucchi, {Silvio E.} and Martinez, {Felipe A.} and {de Boer}, {Rudolf A.} and Hernandez, {Adrian F.} and Shah, {Sanjiv J.} and Magnus Petersson and Langkilde, {Anna Maria} and McMurray, {John J.V.} and Solomon, {Scott D.} and Orly Vardeny",

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year = "2024",

month = apr,

doi = "10.1016/j.jchf.2023.09.007",

language = "English (US)",

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TY - JOUR

T1 - Contemporary Use and Implications of Beta-Blockers in Patients With HFmrEF or HFpEF

T2 - The DELIVER Trial

AU - Peikert, Alexander

AU - Bart, Bradley A.

AU - Vaduganathan, Muthiah

AU - Claggett, Brian L.

AU - Kulac, Ian J.

AU - Kosiborod, Mikhail N.

AU - Desai, Akshay S.

AU - Jhund, Pardeep S.

AU - Lam, Carolyn S.P.

AU - Inzucchi, Silvio E.

AU - Martinez, Felipe A.

AU - de Boer, Rudolf A.

AU - Hernandez, Adrian F.

AU - Shah, Sanjiv J.

AU - Petersson, Magnus

AU - Langkilde, Anna Maria

AU - McMurray, John J.V.

AU - Solomon, Scott D.

AU - Vardeny, Orly

PY - 2024/4

Y1 - 2024/4

N2 - Background: Although beta-blockers are not recommended for the treatment of heart failure with preserved ejection fraction (HFpEF) according to the latest European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines, these therapies remain commonly used for comorbidity management. There has been concern that beta-blockers may adversely influence clinical outcomes by limiting chronotropic response in HFpEF. Objectives: This study sought to examine the contemporary use and implications of beta-blockers in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HFpEF. Methods: In the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial, a total of 6,263 patients with symptomatic heart failure (HF) with a left ventricular ejection fraction (LVEF) >40% were randomized to dapagliflozin or placebo across 20 countries. In this prespecified analysis, efficacy and safety outcomes were examined according to beta-blocker use at randomization. The primary outcome was cardiovascular death or worsening HF. Results: Overall, beta-blockers were used in 5,177 patients (83%), with wide variation by geographic region. Beta-blocker use was associated with a lower risk of the primary outcome in covariate-adjusted models (HR: 0.70; 95% CI: 0.60-0.83). Dapagliflozin consistently reduced the risk of the primary outcome in patients taking beta-blockers (HR: 0.82; 95% CI: 0.72-0.94) and in patients not taking beta-blockers (HR: 0.79; 95% CI: 0.61-1.03; Pinteraction = 0.85), with similar findings for key secondary endpoints. Adverse events were balanced between patients randomized to dapagliflozin and placebo, regardless of background beta-blocker use. Conclusions: In patients with HFmrEF or HFpEF who were enrolled in DELIVER, 4 out of 5 participants were treated with a beta-blocker. Beta-blocker use was not associated with a higher risk of worsening HF or cardiovascular death. Dapagliflozin consistently and safely reduced clinical events, irrespective of background beta-blocker use.

AB - Background: Although beta-blockers are not recommended for the treatment of heart failure with preserved ejection fraction (HFpEF) according to the latest European Society of Cardiology and American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines, these therapies remain commonly used for comorbidity management. There has been concern that beta-blockers may adversely influence clinical outcomes by limiting chronotropic response in HFpEF. Objectives: This study sought to examine the contemporary use and implications of beta-blockers in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HFpEF. Methods: In the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial, a total of 6,263 patients with symptomatic heart failure (HF) with a left ventricular ejection fraction (LVEF) >40% were randomized to dapagliflozin or placebo across 20 countries. In this prespecified analysis, efficacy and safety outcomes were examined according to beta-blocker use at randomization. The primary outcome was cardiovascular death or worsening HF. Results: Overall, beta-blockers were used in 5,177 patients (83%), with wide variation by geographic region. Beta-blocker use was associated with a lower risk of the primary outcome in covariate-adjusted models (HR: 0.70; 95% CI: 0.60-0.83). Dapagliflozin consistently reduced the risk of the primary outcome in patients taking beta-blockers (HR: 0.82; 95% CI: 0.72-0.94) and in patients not taking beta-blockers (HR: 0.79; 95% CI: 0.61-1.03; Pinteraction = 0.85), with similar findings for key secondary endpoints. Adverse events were balanced between patients randomized to dapagliflozin and placebo, regardless of background beta-blocker use. Conclusions: In patients with HFmrEF or HFpEF who were enrolled in DELIVER, 4 out of 5 participants were treated with a beta-blocker. Beta-blocker use was not associated with a higher risk of worsening HF or cardiovascular death. Dapagliflozin consistently and safely reduced clinical events, irrespective of background beta-blocker use.

KW - SGLT2 inhibitors

KW - beta-blockers

KW - heart failure with mildly reduced ejection fraction

KW - heart failure with preserved ejection fraction

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Contemporary Use and Implications of Beta-Blockers in Patients With HFmrEF or HFpEF: The DELIVER Trial

Abstract

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