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.
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 language | English |
|---|---|
| Pages (from-to) | 386-398 |
| Number of pages | 13 |
| Journal | Journal of the American College of Cardiology |
| Volume | 71 |
| Issue number | 4 |
| Early online date | 22 Jan 2018 |
| DOIs | |
| Publication status | Published - 30 Jan 2018 |
Keywords
- ACE inhibitor/ARB
- beta-blocker
- biomarkers
- MRA
- treatment decision
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
