Biomarker-Guided Versus Guideline-Based Treatment of Patients With Heart Failure: Results From BIOSTAT-CHF
journal contributionposted on 12.04.2018, 09:57 by W. Ouwerkerk, A. H. Zwinderman, Leong L. Ng, B. Demissei, H. L. Hillege, F. Zannad, D. J. van Veldhuisen, Nilesh J. Samani, P. Ponikowski, M. Metra, J. M. Ter Maaten, C. C. Lang, P. van der Harst, G. Filippatos, K. Dickstein, J. G. Cleland, S. D. Anker, A. A. Voors
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.