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

Research output: Contribution to journalArticle

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 languageEnglish (US)
JournalEuropean Journal of Heart Failure
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Renin
Heart Failure
Confidence Intervals
Cause of Death
Blood Pressure
Natriuretic Peptides
Glomerular Filtration Rate
Proportional Hazards Models
Signs and Symptoms
Hospitalization

Keywords

  • Acute heart failure
  • Biased ligand
  • Plasma renin activity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Is plasma renin activity associated with worse outcomes in acute heart failure? A secondary analysis from the BLAST-AHF trial. / Rachwan, Rayan Jo; Butler, Javed; Collins, Sean P.; Cotter, Gad; Davison, Beth A.; Senger, Stefanie; Ezekowitz, Justin A.; Filippatos, Gerasimos; Levy, Phillip D.; Metra, Marco; Ponikowski, Piotr; Teerlink, John R.; Voors, Adriaan A.; de Boer, Rudolf A.; Soergel, David G.; Felker, G. Michael; Pang, Peter S.

In: European Journal of Heart Failure, 01.01.2019.

Research output: Contribution to journalArticle

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. https://doi.org/10.1002/ejhf.1607
Rachwan, Rayan Jo ; Butler, Javed ; Collins, Sean P. ; Cotter, Gad ; Davison, Beth A. ; Senger, Stefanie ; Ezekowitz, Justin A. ; Filippatos, Gerasimos ; Levy, Phillip D. ; Metra, Marco ; Ponikowski, Piotr ; Teerlink, John R. ; Voors, Adriaan A. ; de Boer, Rudolf A. ; Soergel, David G. ; Felker, G. Michael ; Pang, Peter S. / Is plasma renin activity associated with worse outcomes in acute heart failure? A secondary analysis from the BLAST-AHF trial. In: European Journal of Heart Failure. 2019.
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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.",
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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.

PY - 2019/1/1

Y1 - 2019/1/1

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.

KW - Acute heart failure

KW - Biased ligand

KW - Plasma renin activity

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