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 journalArticlepeer-review

26 Citations (Scopus)
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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
Issue number4
Early online date22 Jan 2018
Publication statusPublished - 30 Jan 2018


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


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