Is plasma renin activity associated with worse outcomes in acute heart failure? A secondary analysis from the BLAST-AHF trial

Rayan Jo Rachwan; Javed Butler; Sean P. Collins; Gad Cotter; Beth A. Davison; Stefanie Senger; Justin A. Ezekowitz; Gerasimos Filippatos; Phillip D. Levy; Marco Metra; Piotr Ponikowski; John R. Teerlink; Adriaan A. Voors; Rudolf A. de Boer; David G. Soergel; G. Michael Felker; Peter S. Pang

doi:10.1002/ejhf.1607

Is plasma renin activity associated with worse outcomes in acute heart failure? A secondary analysis from the BLAST-AHF trial

Rayan Jo Rachwan, Javed Butler, Sean P. Collins, Gad Cotter, Beth A. Davison, Stefanie Senger, Justin A. Ezekowitz, Gerasimos Filippatos, Phillip D. Levy, Marco Metra, Piotr Ponikowski, John R. Teerlink, Adriaan A. Voors, Rudolf A. de Boer, David G. Soergel, G. Michael Felker, Peter S. Pang^*

^*Corresponding author for this work

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

10 Citations (Scopus)

Abstract

Aims: Neurohormonal activation characterizes chronic heart failure (HF) and is a well-established therapeutic target. Neurohormonal activation may also play a key role in acute HF (AHF). We aim to describe the association between plasma renin activity (PRA) and three AHF outcomes: (i) worsening HF or death through day 5 of hospitalization; (ii) HF rehospitalization or death through day 30; and (iii) all-cause death through day 30. Methods and results: A secondary analysis of the BLAST-AHF trial was performed. Eligible patients had a history of HF, elevated natriuretic peptides, signs and symptoms of HF, systolic blood pressure >120 mmHg, and an estimated glomerular filtration rate between 20–75 mL/min/1.73 m². The primary trial was neutral, with no differential effect of study drug by PRA levels. Baseline PRA levels were grouped into tertiles. Adjusted Cox proportional hazard model determined the association of PRA levels with outcomes (α set at P < 0.05). Of 618 randomized patients, 578 (93.5%) had a baseline PRA. PRA was modestly, but significantly, associated with each outcome without adjustment [worsening HF or death through day 5: hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.01–1.23, P = 0.04; HF rehospitalization or death through day 30: HR 1.13, 95% CI 1.02–1.26, P = 0.02; all-cause death through day 30: HR 1.18, 95% CI 1.02–1.37, P = 0.03]. After multivariable adjustment, PRA was only significantly associated with HF rehospitalization or death through day 30 (HR 1.15, 95% CI 1.01–1.32, P = 0.04). Conclusion: Baseline PRA levels are associated with increased risk for the composite of 30-day HF rehospitalization or death in patients with AHF.

Original language	English
Pages (from-to)	1561-1570
Number of pages	10
Journal	European Journal of Heart Failure
Volume	21
Issue number	12
DOIs	https://doi.org/10.1002/ejhf.1607
Publication status	Published - 1 Dec 2019
Externally published	Yes

Bibliographical note

Funding Information:
The primary BLAST‐AHF trial was supported by Trevena, Inc. However, this secondary analysis was conducted independently.

Funding Information:
R.J.R.: nothing to disclose. J.B.: research grant; significant; NIH, PCORI, European Union. Consultant/advisory board; significant; Amgen, Bayer, Boehringer, Cardiocell, Merck, Novartis, Relypsa, ZS Pharma. S.P.C.: research grant; significant; NIH PCORI, AHA. Consultant/advisory board; significant; Siemens, Cardiorentis, Novartis. G.C.: employment; significant; Momentum Research. B.A.D.: employment; significant; Momentum Research. S.S.: employment; significant; Momentum Research. J.A.E.: research grant; significant; Trevena. G.F.: consultant/advisory board; significant; Bayer, Novartis, Servier. P.D.L.: research grant; significant; NIH, PCORI. Consultant/advisory board; significant; Novartis, Cardiorentis, ZS Pharma. M.M.: consultant/advisory board; significant; Amgen, Bayer, Novartis. P.P.: consultant/advisory board; significant; Bayer, Boerhinger, Novartis. J.R.T.: other research support; significant; Amgen, Bayer, BMS, Medtronic. Consultant/advisory board; significant; Amgen, Bayer, BMS, Cytokinetics, Merck, Novartis, ZS Pharma. A.A.V.: consultant/advisory board; significant; GSK, Novartis, Servier, Boehringer, Merck, Amgen. R.A.d.B.: other research support; significant; Trevena. Consultant/advisory board; significant; Novartis. D.G.S.: employment; significant; Trevena (former), Novartis. G.M.F.: research grant; significant; NIH, AHA, Novartis. Consultant/advisory board; significant; Novartis, Amgen, BMS, GSK, Medtronic. P.S.P.: research grant; significant; AHA, AHRQ, NIH, PCORI. Other research support; significant; Novartis, Roche, BMS, Orthodiagnostics. Consultant/advisory board; significant; BMS, Novartis, Baxter. Conflict of interest:

Publisher Copyright:
© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology

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10.1002/ejhf.1607

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Rachwan, R. J., Butler, J., Collins, S. P., Cotter, G., Davison, B. A., Senger, S., Ezekowitz, J. A., Filippatos, G., Levy, P. D., Metra, M., Ponikowski, P., Teerlink, J. R., Voors, A. A., de Boer, R. A., Soergel, D. G., Felker, G. M., & Pang, P. S. (2019). Is plasma renin activity associated with worse outcomes in acute heart failure? A secondary analysis from the BLAST-AHF trial. European Journal of Heart Failure, 21(12), 1561-1570. https://doi.org/10.1002/ejhf.1607

@article{4327cc33e42a44fc8acc0cb5906d5dc9,

title = "Is plasma renin activity associated with worse outcomes in acute heart failure? A secondary analysis from the BLAST-AHF trial",

abstract = "Aims: Neurohormonal activation characterizes chronic heart failure (HF) and is a well-established therapeutic target. Neurohormonal activation may also play a key role in acute HF (AHF). We aim to describe the association between plasma renin activity (PRA) and three AHF outcomes: (i) worsening HF or death through day 5 of hospitalization; (ii) HF rehospitalization or death through day 30; and (iii) all-cause death through day 30. Methods and results: A secondary analysis of the BLAST-AHF trial was performed. Eligible patients had a history of HF, elevated natriuretic peptides, signs and symptoms of HF, systolic blood pressure >120 mmHg, and an estimated glomerular filtration rate between 20–75 mL/min/1.73 m2. The primary trial was neutral, with no differential effect of study drug by PRA levels. Baseline PRA levels were grouped into tertiles. Adjusted Cox proportional hazard model determined the association of PRA levels with outcomes (α set at P < 0.05). Of 618 randomized patients, 578 (93.5%) had a baseline PRA. PRA was modestly, but significantly, associated with each outcome without adjustment [worsening HF or death through day 5: hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.01–1.23, P = 0.04; HF rehospitalization or death through day 30: HR 1.13, 95% CI 1.02–1.26, P = 0.02; all-cause death through day 30: HR 1.18, 95% CI 1.02–1.37, P = 0.03]. After multivariable adjustment, PRA was only significantly associated with HF rehospitalization or death through day 30 (HR 1.15, 95% CI 1.01–1.32, P = 0.04). Conclusion: Baseline PRA levels are associated with increased risk for the composite of 30-day HF rehospitalization or death in patients with AHF.",

author = "Rachwan, {Rayan Jo} and Javed Butler and Collins, {Sean P.} and Gad Cotter and Davison, {Beth A.} and Stefanie Senger and Ezekowitz, {Justin A.} and Gerasimos Filippatos and Levy, {Phillip D.} and Marco Metra and Piotr Ponikowski and Teerlink, {John R.} and Voors, {Adriaan A.} and {de Boer}, {Rudolf A.} and Soergel, {David G.} and Felker, {G. Michael} and Pang, {Peter S.}",

note = "Funding Information: The primary BLAST‐AHF trial was supported by Trevena, Inc. However, this secondary analysis was conducted independently. Funding Information: R.J.R.: nothing to disclose. J.B.: research grant; significant; NIH, PCORI, European Union. Consultant/advisory board; significant; Amgen, Bayer, Boehringer, Cardiocell, Merck, Novartis, Relypsa, ZS Pharma. S.P.C.: research grant; significant; NIH PCORI, AHA. Consultant/advisory board; significant; Siemens, Cardiorentis, Novartis. G.C.: employment; significant; Momentum Research. B.A.D.: employment; significant; Momentum Research. S.S.: employment; significant; Momentum Research. J.A.E.: research grant; significant; Trevena. G.F.: consultant/advisory board; significant; Bayer, Novartis, Servier. P.D.L.: research grant; significant; NIH, PCORI. Consultant/advisory board; significant; Novartis, Cardiorentis, ZS Pharma. M.M.: consultant/advisory board; significant; Amgen, Bayer, Novartis. P.P.: consultant/advisory board; significant; Bayer, Boerhinger, Novartis. J.R.T.: other research support; significant; Amgen, Bayer, BMS, Medtronic. Consultant/advisory board; significant; Amgen, Bayer, BMS, Cytokinetics, Merck, Novartis, ZS Pharma. A.A.V.: consultant/advisory board; significant; GSK, Novartis, Servier, Boehringer, Merck, Amgen. R.A.d.B.: other research support; significant; Trevena. Consultant/advisory board; significant; Novartis. D.G.S.: employment; significant; Trevena (former), Novartis. G.M.F.: research grant; significant; NIH, AHA, Novartis. Consultant/advisory board; significant; Novartis, Amgen, BMS, GSK, Medtronic. P.S.P.: research grant; significant; AHA, AHRQ, NIH, PCORI. Other research support; significant; Novartis, Roche, BMS, Orthodiagnostics. Consultant/advisory board; significant; BMS, Novartis, Baxter. Conflict of interest: Publisher Copyright: {\textcopyright} 2019 The Authors. European Journal of Heart Failure {\textcopyright} 2019 European Society of Cardiology",

year = "2019",

month = dec,

day = "1",

doi = "10.1002/ejhf.1607",

language = "English",

volume = "21",

pages = "1561--1570",

journal = "European Journal of Heart Failure",

issn = "1388-9842",

publisher = "Wiley-Blackwell",

number = "12",

}

Rachwan, RJ, Butler, J, Collins, SP, Cotter, G, Davison, BA, Senger, S, Ezekowitz, JA, Filippatos, G, Levy, PD, Metra, M, Ponikowski, P, Teerlink, JR, Voors, AA, de Boer, RA, Soergel, DG, Felker, GM & Pang, PS 2019, 'Is plasma renin activity associated with worse outcomes in acute heart failure? A secondary analysis from the BLAST-AHF trial', European Journal of Heart Failure, vol. 21, no. 12, pp. 1561-1570. https://doi.org/10.1002/ejhf.1607

TY - JOUR

T1 - Is plasma renin activity associated with worse outcomes in acute heart failure? A secondary analysis from the BLAST-AHF trial

AU - Rachwan, Rayan Jo

AU - Butler, Javed

AU - Collins, Sean P.

AU - Cotter, Gad

AU - Davison, Beth A.

AU - Senger, Stefanie

AU - Ezekowitz, Justin A.

AU - Filippatos, Gerasimos

AU - Levy, Phillip D.

AU - Metra, Marco

AU - Ponikowski, Piotr

AU - Teerlink, John R.

AU - Voors, Adriaan A.

AU - de Boer, Rudolf A.

AU - Soergel, David G.

AU - Felker, G. Michael

AU - Pang, Peter S.

N1 - Funding Information: The primary BLAST‐AHF trial was supported by Trevena, Inc. However, this secondary analysis was conducted independently. Funding Information: R.J.R.: nothing to disclose. J.B.: research grant; significant; NIH, PCORI, European Union. Consultant/advisory board; significant; Amgen, Bayer, Boehringer, Cardiocell, Merck, Novartis, Relypsa, ZS Pharma. S.P.C.: research grant; significant; NIH PCORI, AHA. Consultant/advisory board; significant; Siemens, Cardiorentis, Novartis. G.C.: employment; significant; Momentum Research. B.A.D.: employment; significant; Momentum Research. S.S.: employment; significant; Momentum Research. J.A.E.: research grant; significant; Trevena. G.F.: consultant/advisory board; significant; Bayer, Novartis, Servier. P.D.L.: research grant; significant; NIH, PCORI. Consultant/advisory board; significant; Novartis, Cardiorentis, ZS Pharma. M.M.: consultant/advisory board; significant; Amgen, Bayer, Novartis. P.P.: consultant/advisory board; significant; Bayer, Boerhinger, Novartis. J.R.T.: other research support; significant; Amgen, Bayer, BMS, Medtronic. Consultant/advisory board; significant; Amgen, Bayer, BMS, Cytokinetics, Merck, Novartis, ZS Pharma. A.A.V.: consultant/advisory board; significant; GSK, Novartis, Servier, Boehringer, Merck, Amgen. R.A.d.B.: other research support; significant; Trevena. Consultant/advisory board; significant; Novartis. D.G.S.: employment; significant; Trevena (former), Novartis. G.M.F.: research grant; significant; NIH, AHA, Novartis. Consultant/advisory board; significant; Novartis, Amgen, BMS, GSK, Medtronic. P.S.P.: research grant; significant; AHA, AHRQ, NIH, PCORI. Other research support; significant; Novartis, Roche, BMS, Orthodiagnostics. Consultant/advisory board; significant; BMS, Novartis, Baxter. Conflict of interest: Publisher Copyright: © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Aims: Neurohormonal activation characterizes chronic heart failure (HF) and is a well-established therapeutic target. Neurohormonal activation may also play a key role in acute HF (AHF). We aim to describe the association between plasma renin activity (PRA) and three AHF outcomes: (i) worsening HF or death through day 5 of hospitalization; (ii) HF rehospitalization or death through day 30; and (iii) all-cause death through day 30. Methods and results: A secondary analysis of the BLAST-AHF trial was performed. Eligible patients had a history of HF, elevated natriuretic peptides, signs and symptoms of HF, systolic blood pressure >120 mmHg, and an estimated glomerular filtration rate between 20–75 mL/min/1.73 m2. The primary trial was neutral, with no differential effect of study drug by PRA levels. Baseline PRA levels were grouped into tertiles. Adjusted Cox proportional hazard model determined the association of PRA levels with outcomes (α set at P < 0.05). Of 618 randomized patients, 578 (93.5%) had a baseline PRA. PRA was modestly, but significantly, associated with each outcome without adjustment [worsening HF or death through day 5: hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.01–1.23, P = 0.04; HF rehospitalization or death through day 30: HR 1.13, 95% CI 1.02–1.26, P = 0.02; all-cause death through day 30: HR 1.18, 95% CI 1.02–1.37, P = 0.03]. After multivariable adjustment, PRA was only significantly associated with HF rehospitalization or death through day 30 (HR 1.15, 95% CI 1.01–1.32, P = 0.04). Conclusion: Baseline PRA levels are associated with increased risk for the composite of 30-day HF rehospitalization or death in patients with AHF.

AB - Aims: Neurohormonal activation characterizes chronic heart failure (HF) and is a well-established therapeutic target. Neurohormonal activation may also play a key role in acute HF (AHF). We aim to describe the association between plasma renin activity (PRA) and three AHF outcomes: (i) worsening HF or death through day 5 of hospitalization; (ii) HF rehospitalization or death through day 30; and (iii) all-cause death through day 30. Methods and results: A secondary analysis of the BLAST-AHF trial was performed. Eligible patients had a history of HF, elevated natriuretic peptides, signs and symptoms of HF, systolic blood pressure >120 mmHg, and an estimated glomerular filtration rate between 20–75 mL/min/1.73 m2. The primary trial was neutral, with no differential effect of study drug by PRA levels. Baseline PRA levels were grouped into tertiles. Adjusted Cox proportional hazard model determined the association of PRA levels with outcomes (α set at P < 0.05). Of 618 randomized patients, 578 (93.5%) had a baseline PRA. PRA was modestly, but significantly, associated with each outcome without adjustment [worsening HF or death through day 5: hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.01–1.23, P = 0.04; HF rehospitalization or death through day 30: HR 1.13, 95% CI 1.02–1.26, P = 0.02; all-cause death through day 30: HR 1.18, 95% CI 1.02–1.37, P = 0.03]. After multivariable adjustment, PRA was only significantly associated with HF rehospitalization or death through day 30 (HR 1.15, 95% CI 1.01–1.32, P = 0.04). Conclusion: Baseline PRA levels are associated with increased risk for the composite of 30-day HF rehospitalization or death in patients with AHF.

UR - http://www.scopus.com/inward/record.url?scp=85074580624&partnerID=8YFLogxK

U2 - 10.1002/ejhf.1607

DO - 10.1002/ejhf.1607

M3 - Article

C2 - 31646707

AN - SCOPUS:85074580624

SN - 1388-9842

VL - 21

SP - 1561

EP - 1570

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

IS - 12

ER -

Is plasma renin activity associated with worse outcomes in acute heart failure? A secondary analysis from the BLAST-AHF trial

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