Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF

Alice M Jackson; Pooja Dewan; Inder S Anand; Jan Bělohlávek; Olof Bengtsson; Rudolf A de Boer; Michael Böhm; David W Boulton; Vijay K Chopra; David L DeMets; Kieran F Docherty; Andrej Dukát; Peter J Greasley; Jonathan G Howlett; Silvio E Inzucchi; Tzvetana Katova; Lars Køber; Mikhail N Kosiborod; Anna Maria Langkilde; Daniel Lindholm; Charlotta E A Ljungman; Felipe A Martinez; Eileen O'Meara; Marc S Sabatine; Mikaela Sjöstrand; Scott D Solomon; Sergey Tereshchenko; Subodh Verma; Pardeep S Jhund; John J V McMurray

doi:10.1161/CIRCULATIONAHA.120.047077

Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF

Alice M Jackson, Pooja Dewan, Inder S Anand, Jan Bělohlávek, Olof Bengtsson, Rudolf A de Boer, Michael Böhm, David W Boulton, Vijay K Chopra, David L DeMets, Kieran F Docherty, Andrej Dukát, Peter J Greasley, Jonathan G Howlett, Silvio E Inzucchi, Tzvetana Katova, Lars Køber, Mikhail N Kosiborod, Anna Maria Langkilde, Daniel LindholmCharlotta E A Ljungman, Felipe A Martinez, Eileen O'Meara, Marc S Sabatine, Mikaela Sjöstrand, Scott D Solomon, Sergey Tereshchenko, Subodh Verma, Pardeep S Jhund, John J V McMurray

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

144 Citationer (Scopus)

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Abstract

BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo.

METHODS: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms.

RESULTS: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization.

CONCLUSIONS: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

Originalsprog	Engelsk
Tidsskrift	Circulation
Vol/bind	142
Udgave nummer	11
Sider (fra-til)	1040-1054
ISSN	0009-7322
DOI	https://doi.org/10.1161/CIRCULATIONAHA.120.047077
Status	Udgivet - 2020

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10.1161/CIRCULATIONAHA.120.047077Licens: CC BY

CIRCULATIONAHA.120.047077Forlagets udgivne version, 808 KBLicens: CC BY

Citationsformater

Jackson, A. M., Dewan, P., Anand, I. S., Bělohlávek, J., Bengtsson, O., de Boer, R. A., Böhm, M., Boulton, D. W., Chopra, V. K., DeMets, D. L., Docherty, K. F., Dukát, A., Greasley, P. J., Howlett, J. G., Inzucchi, S. E., Katova, T., Køber, L., Kosiborod, M. N., Langkilde, A. M., ... McMurray, J. J. V. (2020). Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF. Circulation, 142(11), 1040-1054. https://doi.org/10.1161/CIRCULATIONAHA.120.047077

Jackson, AM, Dewan, P, Anand, IS, Bělohlávek, J, Bengtsson, O, de Boer, RA, Böhm, M, Boulton, DW, Chopra, VK, DeMets, DL, Docherty, KF, Dukát, A, Greasley, PJ, Howlett, JG, Inzucchi, SE, Katova, T, Køber, L, Kosiborod, MN, Langkilde, AM, Lindholm, D, Ljungman, CEA, Martinez, FA, O'Meara, E, Sabatine, MS, Sjöstrand, M, Solomon, SD, Tereshchenko, S, Verma, S, Jhund, PS & McMurray, JJV 2020, 'Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF', Circulation, bind 142, nr. 11, s. 1040-1054. https://doi.org/10.1161/CIRCULATIONAHA.120.047077

@article{b5a0327dd55a4c1391a3be019f63272a,

title = "Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF",

abstract = "BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo.METHODS: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms.RESULTS: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization.CONCLUSIONS: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.",

author = "Jackson, {Alice M} and Pooja Dewan and Anand, {Inder S} and Jan B{\v e}lohl{\'a}vek and Olof Bengtsson and {de Boer}, {Rudolf A} and Michael B{\"o}hm and Boulton, {David W} and Chopra, {Vijay K} and DeMets, {David L} and Docherty, {Kieran F} and Andrej Duk{\'a}t and Greasley, {Peter J} and Howlett, {Jonathan G} and Inzucchi, {Silvio E} and Tzvetana Katova and Lars K{\o}ber and Kosiborod, {Mikhail N} and Langkilde, {Anna Maria} and Daniel Lindholm and Ljungman, {Charlotta E A} and Martinez, {Felipe A} and Eileen O'Meara and Sabatine, {Marc S} and Mikaela Sj{\"o}strand and Solomon, {Scott D} and Sergey Tereshchenko and Subodh Verma and Jhund, {Pardeep S} and McMurray, {John J V}",

year = "2020",

doi = "10.1161/CIRCULATIONAHA.120.047077",

language = "English",

volume = "142",

pages = "1040--1054",

journal = "Circulation",

issn = "0009-7322",

publisher = "Lippincott Williams & Wilkins",

number = "11",

}

TY - JOUR

T1 - Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF

AU - Jackson, Alice M

AU - Dewan, Pooja

AU - Anand, Inder S

AU - Bělohlávek, Jan

AU - Bengtsson, Olof

AU - de Boer, Rudolf A

AU - Böhm, Michael

AU - Boulton, David W

AU - Chopra, Vijay K

AU - DeMets, David L

AU - Docherty, Kieran F

AU - Dukát, Andrej

AU - Greasley, Peter J

AU - Howlett, Jonathan G

AU - Inzucchi, Silvio E

AU - Katova, Tzvetana

AU - Køber, Lars

AU - Kosiborod, Mikhail N

AU - Langkilde, Anna Maria

AU - Lindholm, Daniel

AU - Ljungman, Charlotta E A

AU - Martinez, Felipe A

AU - O'Meara, Eileen

AU - Sabatine, Marc S

AU - Sjöstrand, Mikaela

AU - Solomon, Scott D

AU - Tereshchenko, Sergey

AU - Verma, Subodh

AU - Jhund, Pardeep S

AU - McMurray, John J V

PY - 2020

Y1 - 2020

N2 - BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo.METHODS: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms.RESULTS: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization.CONCLUSIONS: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

AB - BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo.METHODS: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms.RESULTS: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization.CONCLUSIONS: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

U2 - 10.1161/CIRCULATIONAHA.120.047077

DO - 10.1161/CIRCULATIONAHA.120.047077

M3 - Journal article

C2 - 32673497

SN - 0009-7322

VL - 142

SP - 1040

EP - 1054

JO - Circulation

JF - Circulation

IS - 11

ER -