Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF)

Matteo Serenelli; Michael Böhm; Silvio E Inzucchi; Lars Køber; Mikhail N Kosiborod; Felipe A Martinez; Piotr Ponikowski; Marc S Sabatine; Scott D Solomon; David L DeMets; Olof Bengtsson; Mikaela Sjöstrand; Anna Maria Langkilde; Inder S Anand; Chern-En Chiang; Vijay K Chopra; Rudolf A de Boer; Mirta Diez; Andrej Dukát; Junbo Ge; Jonathan G Howlett; Tzvetana Katova; Masafumi Kitakaze; Charlotta E A Ljungman; Subodh Verma; Kieran F Docherty; Pardeep S Jhund; John J V McMurray

doi:10.1093/eurheartj/ehaa496

Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF)

Matteo Serenelli, Michael Böhm, Silvio E Inzucchi, Lars Køber, Mikhail N Kosiborod, Felipe A Martinez, Piotr Ponikowski, Marc S Sabatine, Scott D Solomon, David L DeMets, Olof Bengtsson, Mikaela Sjöstrand, Anna Maria Langkilde, Inder S Anand, Chern-En Chiang, Vijay K Chopra, Rudolf A de Boer, Mirta Diez, Andrej Dukát, Junbo GeJonathan G Howlett, Tzvetana Katova, Masafumi Kitakaze, Charlotta E A Ljungman, Subodh Verma, Kieran F Docherty, Pardeep S Jhund, John J V McMurray

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AIMS: Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).

METHODS AND RESULTS: Key inclusion criteria were: New York Heart Association Class II-IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95 mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP <110 mmHg; 981 ≥ 110 < 120; 1149 ≥ 120 < 130; and 1409 ≥ 130 mmHg. The placebo-corrected reduction in SBP from baseline to 2 weeks with dapagliflozin was -2.54 (-3.33 to -1.76) mmHg (P < 0.001), with a smaller between-treatment difference in patients in the lowest compared to highest SBP category. Patients in the lowest SBP category had a much higher rate (per 100 person-years) of the primary outcome [20.6, 95% confidence interval (95% CI) 17.6-24.2] than those in the highest SBP category (13.8, 11.7-16.4). The benefit and safety of dapagliflozin was consistent across the range of SBP; hazard ratio (95% CI) in each SBP group, lowest to highest: 0.76 (0.60-0.97), 0.76 (0.57-1.02), 0.81 (0.61-1.08), and 0.67 (0.51-0.87), P interaction = 0.78. Study drug discontinuation did not differ between dapagliflozin and placebo across the SBP categories examined.

CONCLUSION: Dapagliflozin had a small effect on SBP in patients with HFrEF and was superior to placebo in improving outcomes, and well tolerated, across the range of SBP included in DAPA-HF.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.

Originalsprog	Engelsk
Tidsskrift	European Heart Journal
Vol/bind	41
Udgave nummer	36
Sider (fra-til)	3402-3418
Antal sider	17
ISSN	0195-668X
DOI	https://doi.org/10.1093/eurheartj/ehaa496
Status	Udgivet - 21 sep. 2020

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10.1093/eurheartj/ehaa496

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Serenelli, M., Böhm, M., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Martinez, F. A., Ponikowski, P., Sabatine, M. S., Solomon, S. D., DeMets, D. L., Bengtsson, O., Sjöstrand, M., Langkilde, A. M., Anand, I. S., Chiang, C-E., Chopra, V. K., de Boer, R. A., Diez, M., Dukát, A., ... McMurray, J. J. V. (2020). Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF). European Heart Journal, 41(36), 3402-3418. https://doi.org/10.1093/eurheartj/ehaa496

Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF). / Serenelli, Matteo; Böhm, Michael; Inzucchi, Silvio E et al.

I: European Heart Journal, Bind 41, Nr. 36, 21.09.2020, s. 3402-3418.

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

Serenelli, M, Böhm, M, Inzucchi, SE, Køber, L, Kosiborod, MN, Martinez, FA, Ponikowski, P, Sabatine, MS, Solomon, SD, DeMets, DL, Bengtsson, O, Sjöstrand, M, Langkilde, AM, Anand, IS, Chiang, C-E, Chopra, VK, de Boer, RA, Diez, M, Dukát, A, Ge, J, Howlett, JG, Katova, T, Kitakaze, M, Ljungman, CEA, Verma, S, Docherty, KF, Jhund, PS & McMurray, JJV 2020, 'Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF)', European Heart Journal, bind 41, nr. 36, s. 3402-3418. https://doi.org/10.1093/eurheartj/ehaa496

@article{a8661c0a3142437e860885dfdc431dda,

title = "Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF)",

abstract = "AIMS: Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).METHODS AND RESULTS: Key inclusion criteria were: New York Heart Association Class II-IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95 mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP <110 mmHg; 981 ≥ 110 < 120; 1149 ≥ 120 < 130; and 1409 ≥ 130 mmHg. The placebo-corrected reduction in SBP from baseline to 2 weeks with dapagliflozin was -2.54 (-3.33 to -1.76) mmHg (P < 0.001), with a smaller between-treatment difference in patients in the lowest compared to highest SBP category. Patients in the lowest SBP category had a much higher rate (per 100 person-years) of the primary outcome [20.6, 95% confidence interval (95% CI) 17.6-24.2] than those in the highest SBP category (13.8, 11.7-16.4). The benefit and safety of dapagliflozin was consistent across the range of SBP; hazard ratio (95% CI) in each SBP group, lowest to highest: 0.76 (0.60-0.97), 0.76 (0.57-1.02), 0.81 (0.61-1.08), and 0.67 (0.51-0.87), P interaction = 0.78. Study drug discontinuation did not differ between dapagliflozin and placebo across the SBP categories examined.CONCLUSION: Dapagliflozin had a small effect on SBP in patients with HFrEF and was superior to placebo in improving outcomes, and well tolerated, across the range of SBP included in DAPA-HF.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.",

author = "Matteo Serenelli and Michael B{\"o}hm and Inzucchi, {Silvio E} and Lars K{\o}ber and Kosiborod, {Mikhail N} and Martinez, {Felipe A} and Piotr Ponikowski and Sabatine, {Marc S} and Solomon, {Scott D} and DeMets, {David L} and Olof Bengtsson and Mikaela Sj{\"o}strand and Langkilde, {Anna Maria} and Anand, {Inder S} and Chern-En Chiang and Chopra, {Vijay K} and {de Boer}, {Rudolf A} and Mirta Diez and Andrej Duk{\'a}t and Junbo Ge and Howlett, {Jonathan G} and Tzvetana Katova and Masafumi Kitakaze and Ljungman, {Charlotta E A} and Subodh Verma and Docherty, {Kieran F} and Jhund, {Pardeep S} and McMurray, {John J V}",

note = "{\textcopyright} The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.",

year = "2020",

month = sep,

day = "21",

doi = "10.1093/eurheartj/ehaa496",

language = "English",

volume = "41",

pages = "3402--3418",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

number = "36",

}

TY - JOUR

T1 - Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF)

AU - Serenelli, Matteo

AU - Böhm, Michael

AU - Inzucchi, Silvio E

AU - Køber, Lars

AU - Kosiborod, Mikhail N

AU - Martinez, Felipe A

AU - Ponikowski, Piotr

AU - Sabatine, Marc S

AU - Solomon, Scott D

AU - DeMets, David L

AU - Bengtsson, Olof

AU - Sjöstrand, Mikaela

AU - Langkilde, Anna Maria

AU - Anand, Inder S

AU - Chiang, Chern-En

AU - Chopra, Vijay K

AU - de Boer, Rudolf A

AU - Diez, Mirta

AU - Dukát, Andrej

AU - Ge, Junbo

AU - Howlett, Jonathan G

AU - Katova, Tzvetana

AU - Kitakaze, Masafumi

AU - Ljungman, Charlotta E A

AU - Verma, Subodh

AU - Docherty, Kieran F

AU - Jhund, Pardeep S

AU - McMurray, John J V

PY - 2020/9/21

Y1 - 2020/9/21

N2 - AIMS: Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).METHODS AND RESULTS: Key inclusion criteria were: New York Heart Association Class II-IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95 mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP <110 mmHg; 981 ≥ 110 < 120; 1149 ≥ 120 < 130; and 1409 ≥ 130 mmHg. The placebo-corrected reduction in SBP from baseline to 2 weeks with dapagliflozin was -2.54 (-3.33 to -1.76) mmHg (P < 0.001), with a smaller between-treatment difference in patients in the lowest compared to highest SBP category. Patients in the lowest SBP category had a much higher rate (per 100 person-years) of the primary outcome [20.6, 95% confidence interval (95% CI) 17.6-24.2] than those in the highest SBP category (13.8, 11.7-16.4). The benefit and safety of dapagliflozin was consistent across the range of SBP; hazard ratio (95% CI) in each SBP group, lowest to highest: 0.76 (0.60-0.97), 0.76 (0.57-1.02), 0.81 (0.61-1.08), and 0.67 (0.51-0.87), P interaction = 0.78. Study drug discontinuation did not differ between dapagliflozin and placebo across the SBP categories examined.CONCLUSION: Dapagliflozin had a small effect on SBP in patients with HFrEF and was superior to placebo in improving outcomes, and well tolerated, across the range of SBP included in DAPA-HF.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.

AB - AIMS: Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).METHODS AND RESULTS: Key inclusion criteria were: New York Heart Association Class II-IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95 mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP <110 mmHg; 981 ≥ 110 < 120; 1149 ≥ 120 < 130; and 1409 ≥ 130 mmHg. The placebo-corrected reduction in SBP from baseline to 2 weeks with dapagliflozin was -2.54 (-3.33 to -1.76) mmHg (P < 0.001), with a smaller between-treatment difference in patients in the lowest compared to highest SBP category. Patients in the lowest SBP category had a much higher rate (per 100 person-years) of the primary outcome [20.6, 95% confidence interval (95% CI) 17.6-24.2] than those in the highest SBP category (13.8, 11.7-16.4). The benefit and safety of dapagliflozin was consistent across the range of SBP; hazard ratio (95% CI) in each SBP group, lowest to highest: 0.76 (0.60-0.97), 0.76 (0.57-1.02), 0.81 (0.61-1.08), and 0.67 (0.51-0.87), P interaction = 0.78. Study drug discontinuation did not differ between dapagliflozin and placebo across the SBP categories examined.CONCLUSION: Dapagliflozin had a small effect on SBP in patients with HFrEF and was superior to placebo in improving outcomes, and well tolerated, across the range of SBP included in DAPA-HF.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.

U2 - 10.1093/eurheartj/ehaa496

DO - 10.1093/eurheartj/ehaa496

M3 - Journal article

C2 - 32820334

VL - 41

SP - 3402

EP - 3418

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

IS - 36

ER -

Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF)

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