Efficacy and safety of dapagliflozin according to aetiology in heart failure with reduced ejection fraction: insights from the DAPA-HF trial

Jawad H Butt; Jose C Nicolau; Subodh Verma; Kieran F Docherty; Mark C Petrie; Silvio E Inzucchi; Morten Schou; Mikhail N Kosiborod; Anna Maria Langkilde; Felipe A Martinez; Piotr Ponikowski; Marc S Sabatine; Mikaela Sjöstrand; Scott D Solomon; Olof Bengtsson; Pardeep S Jhund; John J V McMurray; Lars Køber

doi:10.1002/ejhf.2124

Efficacy and safety of dapagliflozin according to aetiology in heart failure with reduced ejection fraction: insights from the DAPA-HF trial

Jawad H Butt, Jose C Nicolau, Subodh Verma, Kieran F Docherty, Mark C Petrie, Silvio E Inzucchi, Morten Schou, Mikhail N Kosiborod, Anna Maria Langkilde, Felipe A Martinez, Piotr Ponikowski, Marc S Sabatine, Mikaela Sjöstrand, Scott D Solomon, Olof Bengtsson, Pardeep S Jhund, John J V McMurray, Lars Køber

41 Citations (Scopus)

Abstract

AIMS: We examined the efficacy and safety of dapagliflozin, compared with placebo, according to aetiology in patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF).

METHODS AND RESULTS: Aetiology was investigator-reported and categorized as ischaemic or non-ischaemic. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. A total of 4744 patients were randomized in DAPA-HF, of whom 2674 (56.4%) patients had an ischaemic aetiology. Participants with an ischaemic aetiology had a higher risk of cardiovascular mortality [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.13-1.63], but lower risk of HF hospitalization (HR 0.83, 95% CI 0.70-0.98) than non-ischaemic patients. Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in both patients with ischaemic and non-ischaemic aetiology (HR 0.77, 95% CI 0.65-0.92, and HR 0.71, 95% CI 0.58-0.87, respectively; P for interaction = 0.55). Consistent benefits were observed for the components of the primary outcome and all-cause mortality. Dapagliflozin, as compared with placebo, increased the proportion of patients with an improvement of Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) of ≥5 points (P for interaction = 0.32) and decreased the proportion with a deterioration in KCCQ-TSS of ≥5 points (P for interaction = 0.76), irrespective of aetiology. Study drug discontinuation and serious adverse events were similar according to treatment groups, irrespective of aetiology.

CONCLUSIONS: Dapagliflozin reduced the risk of worsening HF and death, and improved symptoms, similarly in patients with ischaemic and non-ischaemic aetiology. In addition, dapagliflozin was safe and well-tolerated, irrespective of aetiology.

Original language	English
Journal	European Journal of Heart Failure
Volume	23
Issue number	4
Pages (from-to)	601-613
Number of pages	13
ISSN	1388-9842
DOIs	https://doi.org/10.1002/ejhf.2124
Publication status	Published - Apr 2021

Keywords

Aetiology
Dapagliflozin
Heart failure
Randomized controlled trial

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10.1002/ejhf.2124

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Butt, J. H., Nicolau, J. C., Verma, S., Docherty, K. F., Petrie, M. C., Inzucchi, S. E., Schou, M., Kosiborod, M. N., Langkilde, A. M., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Sjöstrand, M., Solomon, S. D., Bengtsson, O., Jhund, P. S., McMurray, J. J. V., & Køber, L. (2021). Efficacy and safety of dapagliflozin according to aetiology in heart failure with reduced ejection fraction: insights from the DAPA-HF trial. European Journal of Heart Failure, 23(4), 601-613. https://doi.org/10.1002/ejhf.2124

Butt, JH, Nicolau, JC, Verma, S, Docherty, KF, Petrie, MC, Inzucchi, SE, Schou, M, Kosiborod, MN, Langkilde, AM, Martinez, FA, Ponikowski, P, Sabatine, MS, Sjöstrand, M, Solomon, SD, Bengtsson, O, Jhund, PS, McMurray, JJV & Køber, L 2021, 'Efficacy and safety of dapagliflozin according to aetiology in heart failure with reduced ejection fraction: insights from the DAPA-HF trial', European Journal of Heart Failure, vol. 23, no. 4, pp. 601-613. https://doi.org/10.1002/ejhf.2124

@article{2dc01a286cfe46b28b85cc5025891f87,

title = "Efficacy and safety of dapagliflozin according to aetiology in heart failure with reduced ejection fraction: insights from the DAPA-HF trial",

abstract = "AIMS: We examined the efficacy and safety of dapagliflozin, compared with placebo, according to aetiology in patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF).METHODS AND RESULTS: Aetiology was investigator-reported and categorized as ischaemic or non-ischaemic. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. A total of 4744 patients were randomized in DAPA-HF, of whom 2674 (56.4\%) patients had an ischaemic aetiology. Participants with an ischaemic aetiology had a higher risk of cardiovascular mortality [hazard ratio (HR) 1.35, 95\% confidence interval (CI) 1.13-1.63], but lower risk of HF hospitalization (HR 0.83, 95\% CI 0.70-0.98) than non-ischaemic patients. Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in both patients with ischaemic and non-ischaemic aetiology (HR 0.77, 95\% CI 0.65-0.92, and HR 0.71, 95\% CI 0.58-0.87, respectively; P for interaction = 0.55). Consistent benefits were observed for the components of the primary outcome and all-cause mortality. Dapagliflozin, as compared with placebo, increased the proportion of patients with an improvement of Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) of ≥5 points (P for interaction = 0.32) and decreased the proportion with a deterioration in KCCQ-TSS of ≥5 points (P for interaction = 0.76), irrespective of aetiology. Study drug discontinuation and serious adverse events were similar according to treatment groups, irrespective of aetiology.CONCLUSIONS: Dapagliflozin reduced the risk of worsening HF and death, and improved symptoms, similarly in patients with ischaemic and non-ischaemic aetiology. In addition, dapagliflozin was safe and well-tolerated, irrespective of aetiology.",

keywords = "Aetiology, Dapagliflozin, Heart failure, Randomized controlled trial",

author = "Butt, \{Jawad H\} and Nicolau, \{Jose C\} and Subodh Verma and Docherty, \{Kieran F\} and Petrie, \{Mark C\} and Inzucchi, \{Silvio E\} and Morten Schou and Kosiborod, \{Mikhail N\} and Langkilde, \{Anna Maria\} and Martinez, \{Felipe A\} and Piotr Ponikowski and Sabatine, \{Marc S\} and Mikaela Sj{\"o}strand and Solomon, \{Scott D\} and Olof Bengtsson and Jhund, \{Pardeep S\} and McMurray, \{John J V\} and Lars K{\o}ber",

note = "{\textcopyright} 2021 The Authors. European Journal of Heart Failure published by John Wiley \& Sons Ltd on behalf of European Society of Cardiology.",

year = "2021",

month = apr,

doi = "10.1002/ejhf.2124",

language = "English",

volume = "23",

pages = "601--613",

journal = "European Journal of Heart Failure",

issn = "1388-9842",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

T1 - Efficacy and safety of dapagliflozin according to aetiology in heart failure with reduced ejection fraction

T2 - insights from the DAPA-HF trial

AU - Butt, Jawad H

AU - Nicolau, Jose C

AU - Verma, Subodh

AU - Docherty, Kieran F

AU - Petrie, Mark C

AU - Inzucchi, Silvio E

AU - Schou, Morten

AU - Kosiborod, Mikhail N

AU - Langkilde, Anna Maria

AU - Martinez, Felipe A

AU - Ponikowski, Piotr

AU - Sabatine, Marc S

AU - Sjöstrand, Mikaela

AU - Solomon, Scott D

AU - Bengtsson, Olof

AU - Jhund, Pardeep S

AU - McMurray, John J V

AU - Køber, Lars

PY - 2021/4

Y1 - 2021/4

N2 - AIMS: We examined the efficacy and safety of dapagliflozin, compared with placebo, according to aetiology in patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF).METHODS AND RESULTS: Aetiology was investigator-reported and categorized as ischaemic or non-ischaemic. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. A total of 4744 patients were randomized in DAPA-HF, of whom 2674 (56.4%) patients had an ischaemic aetiology. Participants with an ischaemic aetiology had a higher risk of cardiovascular mortality [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.13-1.63], but lower risk of HF hospitalization (HR 0.83, 95% CI 0.70-0.98) than non-ischaemic patients. Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in both patients with ischaemic and non-ischaemic aetiology (HR 0.77, 95% CI 0.65-0.92, and HR 0.71, 95% CI 0.58-0.87, respectively; P for interaction = 0.55). Consistent benefits were observed for the components of the primary outcome and all-cause mortality. Dapagliflozin, as compared with placebo, increased the proportion of patients with an improvement of Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) of ≥5 points (P for interaction = 0.32) and decreased the proportion with a deterioration in KCCQ-TSS of ≥5 points (P for interaction = 0.76), irrespective of aetiology. Study drug discontinuation and serious adverse events were similar according to treatment groups, irrespective of aetiology.CONCLUSIONS: Dapagliflozin reduced the risk of worsening HF and death, and improved symptoms, similarly in patients with ischaemic and non-ischaemic aetiology. In addition, dapagliflozin was safe and well-tolerated, irrespective of aetiology.

AB - AIMS: We examined the efficacy and safety of dapagliflozin, compared with placebo, according to aetiology in patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF).METHODS AND RESULTS: Aetiology was investigator-reported and categorized as ischaemic or non-ischaemic. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. A total of 4744 patients were randomized in DAPA-HF, of whom 2674 (56.4%) patients had an ischaemic aetiology. Participants with an ischaemic aetiology had a higher risk of cardiovascular mortality [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.13-1.63], but lower risk of HF hospitalization (HR 0.83, 95% CI 0.70-0.98) than non-ischaemic patients. Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in both patients with ischaemic and non-ischaemic aetiology (HR 0.77, 95% CI 0.65-0.92, and HR 0.71, 95% CI 0.58-0.87, respectively; P for interaction = 0.55). Consistent benefits were observed for the components of the primary outcome and all-cause mortality. Dapagliflozin, as compared with placebo, increased the proportion of patients with an improvement of Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) of ≥5 points (P for interaction = 0.32) and decreased the proportion with a deterioration in KCCQ-TSS of ≥5 points (P for interaction = 0.76), irrespective of aetiology. Study drug discontinuation and serious adverse events were similar according to treatment groups, irrespective of aetiology.CONCLUSIONS: Dapagliflozin reduced the risk of worsening HF and death, and improved symptoms, similarly in patients with ischaemic and non-ischaemic aetiology. In addition, dapagliflozin was safe and well-tolerated, irrespective of aetiology.

KW - Aetiology

KW - Dapagliflozin

KW - Heart failure

KW - Randomized controlled trial

UR - https://www.scopus.com/pages/publications/85102243941

U2 - 10.1002/ejhf.2124

DO - 10.1002/ejhf.2124

M3 - Journal article

C2 - 33594755

SN - 1388-9842

VL - 23

SP - 601

EP - 613

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

IS - 4

ER -

Efficacy and safety of dapagliflozin according to aetiology in heart failure with reduced ejection fraction: insights from the DAPA-HF trial

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