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 C
AU - van der Harst, Pim
AU - Filippatos, Gerasimos
AU - Dickstein, Kenneth
AU - Cleland, John G
AU - Anker, Stefan D
AU - Voors, Adriaan A
N1 - Funding Information:
This work was supported by a grant from the European Commission (FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29). Dr. Metra has received consulting honoraria from Amgen, Bayer, Novartis, and Servier; and speaker fees from Abbott Vascular, Bayer, and ResMed. Dr. Lang has received consultancy fees and/or research grants from Amgen, AstraZeneca, MSD, Novartis, and Servier. Dr. van der Harst has received a research grant from Abbott. Dr. Filippatos has received fees and/or research grants from Novartis, Bayer, Cardiorentis, Vifor, Servier, Alere, and Abbott. Dr. Dickstein has received honoraria and/or research support from Medtronic, Boston Scientific, St. Jude Medical, Biotronik, Sorin, Merck, Novartis, Amgen, Boehringer Ingelheim, AstraZeneca, Pfizer, Bayer, GlaxoSmithKline, Roche, Sanofi, Abbott, Otsuka, Leo, Servier, and Bristol-Myers Squibb. Dr. Cleland has received grant support from Amgen, Novartis, and Stealth Biopharmaceuticals; and honoraria from Servier. Dr. Anker has received grants from Vifor and Abbott Vascular; and consulting fees from Vifor, Bayer, Boehringer Ingelheim, Brahms, Cardiorentis, Janssen, Novartis, Relypsa, Servier, Stealth Peptides, and ZS Pharma. Dr. Voors has received consultancy fees and/or research grants from Alere, Amgen, Bayer, Boehringer Ingelheim, Cardio3Biosciences, Celladon, GlaxoSmithKline, Merck/MSD, Novartis, Servier, Stealth Peptides, Singulex, Sphingotec, Trevena, Vifor, and ZS Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Publisher Copyright:
© 2018 American College of Cardiology Foundation
PY - 2018/1/30
Y1 - 2018/1/30
N2 - BACKGROUND: Heart failure guidelines recommend up-titration of angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) to doses used in randomized clinical trials, but these recommended doses are often not reached. Up-titration may, however, not be necessary in all patients.OBJECTIVES: This study sought to establish the role of blood biomarkers to determine which patients should or should not be up-titrated.METHODS: Clinical outcomes of 2,516 patients with worsening heart failure from the BIOSTAT-CHF (BIOlogy Study to Tailored Treatment in Chronic Heart Failure) were compared between 3 theoretical treatment scenarios: scenario A, in which all patients are up-titrated to >50% of recommended doses; scenario B, in which patients are up-titrated according to a biomarker-based treatment selection model; and scenario C, in which no patient is up-titrated to >50% of recommended doses. The study conducted multivariable Cox regression using 161 biomarkers and their interaction with treatment, weighted for treatment-indication bias to estimate the expected number of deaths or heart failure hospitalizations at 24 months for all 3 scenarios.RESULTS: Estimated death or hospitalization rates in 1,802 patients with available (bio)markers were 16%, 16%, and 26%, respectively, in the ACE inhibitor/ARB up-titration scenarios 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, respectively. Similar numbers were 9.9, 4.7, and 13.1 if up-titration treatment decision was based on a biomarker-based treatment selection model.CONCLUSIONS: Up-titrating patients with heart failure based on biomarker values might have resulted in fewer deaths or hospitalizations compared with a hypothetical scenario in which all patients were successfully up-titrated.
AB - BACKGROUND: Heart failure guidelines recommend up-titration of angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) to doses used in randomized clinical trials, but these recommended doses are often not reached. Up-titration may, however, not be necessary in all patients.OBJECTIVES: This study sought to establish the role of blood biomarkers to determine which patients should or should not be up-titrated.METHODS: Clinical outcomes of 2,516 patients with worsening heart failure from the BIOSTAT-CHF (BIOlogy Study to Tailored Treatment in Chronic Heart Failure) were compared between 3 theoretical treatment scenarios: scenario A, in which all patients are up-titrated to >50% of recommended doses; scenario B, in which patients are up-titrated according to a biomarker-based treatment selection model; and scenario C, in which no patient is up-titrated to >50% of recommended doses. The study conducted multivariable Cox regression using 161 biomarkers and their interaction with treatment, weighted for treatment-indication bias to estimate the expected number of deaths or heart failure hospitalizations at 24 months for all 3 scenarios.RESULTS: Estimated death or hospitalization rates in 1,802 patients with available (bio)markers were 16%, 16%, and 26%, respectively, in the ACE inhibitor/ARB up-titration scenarios 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, respectively. Similar numbers were 9.9, 4.7, and 13.1 if up-titration treatment decision was based on a biomarker-based treatment selection model.CONCLUSIONS: Up-titrating patients with heart failure based on biomarker values might have resulted in fewer deaths or hospitalizations compared with a hypothetical scenario in which all patients were successfully up-titrated.
KW - Adrenergic beta-Antagonists/administration & dosage
KW - Aged
KW - Aged, 80 and over
KW - Angiotensin Receptor Antagonists/administration & dosage
KW - Angiotensin-Converting Enzyme Inhibitors/administration & dosage
KW - Biomarkers/blood
KW - Computer Simulation
KW - Dose-Response Relationship, Drug
KW - Female
KW - Heart Failure/blood
KW - Humans
KW - Male
KW - Middle Aged
KW - Mineralocorticoid Receptor Antagonists/administration & dosage
KW - Patient Selection
KW - Practice Guidelines as Topic
KW - Prospective Studies
KW - ACE inhibitor/ARB
KW - beta-blocker
KW - treatment decision
KW - biomarkers
KW - MRA
UR - http://www.scopus.com/inward/record.url?scp=85044438363&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2017.11.041
DO - 10.1016/j.jacc.2017.11.041
M3 - Article
C2 - 29389354
SN - 0735-1097
VL - 71
SP - 386
EP - 398
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 4
ER -