Biomarker-Guided Versus Guideline-Based Treatment of Patients With Heart Failure: Results From BIOSTAT-CHF

Wouter Ouwerkerk (Lead / Corresponding author), Aeilko H. Zwinderman, Leong L. Ng, Biniyam Demissei, Hans L. Hillege, Faiez Zannad, Dirk J. van Veldhuisen, Nilesh J. Samani, Piotr Ponikowski, Marco Metra, Jozine M. ter Maaten, Chim Lang, Pim van der Harst, Gerasimos S. Filippatos, Kenneth Dickstein, John G. F. Cleland, Stefan D. Anker, Adriaan A. Voors

Research output: Contribution to journalArticle

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Abstract

Background: Heart failure guidelines recommend up-titration of ACE-inhibitors/ARBs, beta-blockers and MRA’s to doses used in randomized clinical trials, but these recommended doses are often not reached. Up-titration might however not be necessary in all patients. We aimed to establish the role of blood biomarkers to determine which patients should or should not be up-titrated.

Methods: Clinical outcomes of 2516 patients with worsening heart failure from BIOSTAT-CHF were compared between 3 theoretical treatment scenarios: A) all patients are up-titrated to >50% of recommended doses; B) patients are up-titrated according to a biomarker-based treatment-selection model; C) no patient is up-titrated to >50% of recommended doses. We conducted multivariable Cox regression using 161 biomarkers and their interaction with treatment, weighted for treatment-indication bias to estimate the expected number of deaths and/or heart-failure hospitalizations at 24 months for all three scenarios.

Results: Estimated death/hospitalization rates in 1802 patients with available (bio)markers were 16%, 16%, and 26% respectively in ACE-inhibitor/ARB up-titration scenario A, B and C. Similar rates for beta-blocker and MRA up-titration scenarios A, B, and C were 23%, 19%, and 24%, and 12%, 11% and 24 %, respectively. If up-titration was successful in all patients, an estimated 9.8, 1.3 and 12.3 events per 100 treated patients could be prevented at 24 months by ACE-inhibitor/ARB, beta-blocker and MRA therapy. Similar numbers were 9.9, 4.7 and 13.1 if up-titration treatment decision was based on a biomarker-based treatment-selection model.
Conclusion: Up-titrating patients with heart failure based on biomarker values might have resulted in fewer deaths and/or hospitalizations compared to a hypothetical scenario in which all patients were successfully up-titrated.
Original languageEnglish
Pages (from-to)386-398
Number of pages13
JournalJournal of the American College of Cardiology
Volume71
Issue number4
Early online date22 Jan 2018
DOIs
Publication statusPublished - 30 Jan 2018

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Heart Failure
Biomarkers
Guidelines
Angiotensin-Converting Enzyme Inhibitors
Therapeutics
Hospitalization
Randomized Controlled Trials
Mortality

Keywords

  • ACE inhibitor/ARB
  • beta-blocker
  • biomarkers
  • MRA
  • treatment decision

Cite this

Ouwerkerk, W., Zwinderman, A. H., Ng, L. L., Demissei, B., Hillege, H. L., Zannad, F., ... Voors, A. A. (2018). Biomarker-Guided Versus Guideline-Based Treatment of Patients With Heart Failure: Results From BIOSTAT-CHF. Journal of the American College of Cardiology, 71(4), 386-398. https://doi.org/10.1016/j.jacc.2017.11.041
Ouwerkerk, Wouter ; Zwinderman, Aeilko H. ; Ng, Leong L. ; Demissei, Biniyam ; Hillege, Hans L. ; Zannad, Faiez ; van Veldhuisen, Dirk J. ; Samani, Nilesh J. ; Ponikowski, Piotr ; Metra, Marco ; ter Maaten, Jozine M. ; Lang, Chim ; van der Harst, Pim ; Filippatos, Gerasimos S. ; Dickstein, Kenneth ; Cleland, John G. F. ; Anker, Stefan D. ; Voors, Adriaan A. / Biomarker-Guided Versus Guideline-Based Treatment of Patients With Heart Failure : Results From BIOSTAT-CHF. In: Journal of the American College of Cardiology. 2018 ; Vol. 71, No. 4. pp. 386-398.
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title = "Biomarker-Guided Versus Guideline-Based Treatment of Patients With Heart Failure: Results From BIOSTAT-CHF",
abstract = "Background: Heart failure guidelines recommend up-titration of ACE-inhibitors/ARBs, beta-blockers and MRA’s to doses used in randomized clinical trials, but these recommended doses are often not reached. Up-titration might however not be necessary in all patients. We aimed to establish the role of blood biomarkers to determine which patients should or should not be up-titrated. Methods: Clinical outcomes of 2516 patients with worsening heart failure from BIOSTAT-CHF were compared between 3 theoretical treatment scenarios: A) all patients are up-titrated to >50{\%} of recommended doses; B) patients are up-titrated according to a biomarker-based treatment-selection model; C) no patient is up-titrated to >50{\%} of recommended doses. We conducted multivariable Cox regression using 161 biomarkers and their interaction with treatment, weighted for treatment-indication bias to estimate the expected number of deaths and/or heart-failure hospitalizations at 24 months for all three scenarios.Results: Estimated death/hospitalization rates in 1802 patients with available (bio)markers were 16{\%}, 16{\%}, and 26{\%} respectively in ACE-inhibitor/ARB up-titration scenario A, B and C. Similar rates for beta-blocker and MRA up-titration scenarios A, B, and C were 23{\%}, 19{\%}, and 24{\%}, and 12{\%}, 11{\%} and 24 {\%}, respectively. If up-titration was successful in all patients, an estimated 9.8, 1.3 and 12.3 events per 100 treated patients could be prevented at 24 months by ACE-inhibitor/ARB, beta-blocker and MRA therapy. Similar numbers were 9.9, 4.7 and 13.1 if up-titration treatment decision was based on a biomarker-based treatment-selection model.Conclusion: Up-titrating patients with heart failure based on biomarker values might have resulted in fewer deaths and/or hospitalizations compared to a hypothetical scenario in which all patients were successfully up-titrated.",
keywords = "ACE inhibitor/ARB, beta-blocker, biomarkers, MRA, treatment decision",
author = "Wouter Ouwerkerk and Zwinderman, {Aeilko H.} and Ng, {Leong L.} and Biniyam Demissei and Hillege, {Hans L.} and Faiez Zannad and {van Veldhuisen}, {Dirk J.} and Samani, {Nilesh J.} and Piotr Ponikowski and Marco Metra and {ter Maaten}, {Jozine M.} and Chim Lang and {van der Harst}, Pim and Filippatos, {Gerasimos S.} and Kenneth Dickstein and Cleland, {John G. F.} and Anker, {Stefan D.} and Voors, {Adriaan A.}",
note = "This work was supported by a grant from the European Commission [FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29]",
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Ouwerkerk, W, Zwinderman, AH, Ng, LL, Demissei, B, Hillege, HL, Zannad, F, van Veldhuisen, DJ, Samani, NJ, Ponikowski, P, Metra, M, ter Maaten, JM, Lang, C, van der Harst, P, Filippatos, GS, Dickstein, K, Cleland, JGF, Anker, SD & Voors, AA 2018, 'Biomarker-Guided Versus Guideline-Based Treatment of Patients With Heart Failure: Results From BIOSTAT-CHF', Journal of the American College of Cardiology, vol. 71, no. 4, pp. 386-398. https://doi.org/10.1016/j.jacc.2017.11.041

Biomarker-Guided Versus Guideline-Based Treatment of Patients With Heart Failure : Results From BIOSTAT-CHF. / Ouwerkerk, Wouter (Lead / Corresponding author); Zwinderman, Aeilko H.; Ng, Leong L.; Demissei, Biniyam; Hillege, Hans L.; Zannad, Faiez; van Veldhuisen, Dirk J.; Samani, Nilesh J.; Ponikowski, Piotr; Metra, Marco; ter Maaten, Jozine M.; Lang, Chim; van der Harst, Pim; Filippatos, Gerasimos S.; Dickstein, Kenneth; Cleland, John G. F.; Anker, Stefan D.; Voors, Adriaan A.

In: Journal of the American College of Cardiology, Vol. 71, No. 4, 30.01.2018, p. 386-398.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Biomarker-Guided Versus Guideline-Based Treatment of Patients With Heart Failure

T2 - Results From BIOSTAT-CHF

AU - Ouwerkerk, Wouter

AU - Zwinderman, Aeilko H.

AU - Ng, Leong L.

AU - Demissei, Biniyam

AU - Hillege, Hans L.

AU - Zannad, Faiez

AU - van Veldhuisen, Dirk J.

AU - Samani, Nilesh J.

AU - Ponikowski, Piotr

AU - Metra, Marco

AU - ter Maaten, Jozine M.

AU - Lang, Chim

AU - van der Harst, Pim

AU - Filippatos, Gerasimos S.

AU - Dickstein, Kenneth

AU - Cleland, John G. F.

AU - Anker, Stefan D.

AU - Voors, Adriaan A.

N1 - This work was supported by a grant from the European Commission [FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29]

PY - 2018/1/30

Y1 - 2018/1/30

N2 - Background: Heart failure guidelines recommend up-titration of ACE-inhibitors/ARBs, beta-blockers and MRA’s to doses used in randomized clinical trials, but these recommended doses are often not reached. Up-titration might however not be necessary in all patients. We aimed to establish the role of blood biomarkers to determine which patients should or should not be up-titrated. Methods: Clinical outcomes of 2516 patients with worsening heart failure from BIOSTAT-CHF were compared between 3 theoretical treatment scenarios: A) all patients are up-titrated to >50% of recommended doses; B) patients are up-titrated according to a biomarker-based treatment-selection model; C) no patient is up-titrated to >50% of recommended doses. We conducted multivariable Cox regression using 161 biomarkers and their interaction with treatment, weighted for treatment-indication bias to estimate the expected number of deaths and/or heart-failure hospitalizations at 24 months for all three scenarios.Results: Estimated death/hospitalization rates in 1802 patients with available (bio)markers were 16%, 16%, and 26% respectively in ACE-inhibitor/ARB up-titration scenario A, B and C. Similar rates for beta-blocker and MRA up-titration scenarios A, B, and C were 23%, 19%, and 24%, and 12%, 11% and 24 %, respectively. If up-titration was successful in all patients, an estimated 9.8, 1.3 and 12.3 events per 100 treated patients could be prevented at 24 months by ACE-inhibitor/ARB, beta-blocker and MRA therapy. Similar numbers were 9.9, 4.7 and 13.1 if up-titration treatment decision was based on a biomarker-based treatment-selection model.Conclusion: Up-titrating patients with heart failure based on biomarker values might have resulted in fewer deaths and/or hospitalizations compared to a hypothetical scenario in which all patients were successfully up-titrated.

AB - Background: Heart failure guidelines recommend up-titration of ACE-inhibitors/ARBs, beta-blockers and MRA’s to doses used in randomized clinical trials, but these recommended doses are often not reached. Up-titration might however not be necessary in all patients. We aimed to establish the role of blood biomarkers to determine which patients should or should not be up-titrated. Methods: Clinical outcomes of 2516 patients with worsening heart failure from BIOSTAT-CHF were compared between 3 theoretical treatment scenarios: A) all patients are up-titrated to >50% of recommended doses; B) patients are up-titrated according to a biomarker-based treatment-selection model; C) no patient is up-titrated to >50% of recommended doses. We conducted multivariable Cox regression using 161 biomarkers and their interaction with treatment, weighted for treatment-indication bias to estimate the expected number of deaths and/or heart-failure hospitalizations at 24 months for all three scenarios.Results: Estimated death/hospitalization rates in 1802 patients with available (bio)markers were 16%, 16%, and 26% respectively in ACE-inhibitor/ARB up-titration scenario A, B and C. Similar rates for beta-blocker and MRA up-titration scenarios A, B, and C were 23%, 19%, and 24%, and 12%, 11% and 24 %, respectively. If up-titration was successful in all patients, an estimated 9.8, 1.3 and 12.3 events per 100 treated patients could be prevented at 24 months by ACE-inhibitor/ARB, beta-blocker and MRA therapy. Similar numbers were 9.9, 4.7 and 13.1 if up-titration treatment decision was based on a biomarker-based treatment-selection model.Conclusion: Up-titrating patients with heart failure based on biomarker values might have resulted in fewer deaths and/or hospitalizations compared to a hypothetical scenario in which all patients were successfully up-titrated.

KW - ACE inhibitor/ARB

KW - beta-blocker

KW - biomarkers

KW - MRA

KW - treatment decision

U2 - 10.1016/j.jacc.2017.11.041

DO - 10.1016/j.jacc.2017.11.041

M3 - Article

C2 - 29389354

VL - 71

SP - 386

EP - 398

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 4

ER -