TY - JOUR
T1 - Association between up-titration of medical therapy and total hospitalizations and mortality in patients with recent worsening heart failure across the ejection fraction spectrum
AU - Bistola, Vasiliki
AU - Simitsis, Panagiotis
AU - Parissis, John
AU - Ouwerkerk, Wouter
AU - van Veldhuisen, Dirk J.
AU - Cleland, John G.
AU - Anker, Stefan D.
AU - Samani, Nilesh J.
AU - Metra, Marco
AU - Zannad, Faiez
AU - Polyzogopoulou, Eftihia
AU - Keramida, Kalliopi
AU - Farmakis, Dimitrios
AU - Voors, Adriaan A.
AU - Filippatos, Gerasimos
N1 - Funding Information: This project was funded by a grant from the European Commission (FP7‐242209‐BIOSTAT‐CHF; EudraCT 2010‐020808‐29). Funding Information: This project was funded by a grant from the European Commission (FP7-242209-BIOSTAT-CHF; EudraCT 2010-020808-29). Conflict of interest: V.B. reports honoraria for lectures from AstraZeneca, Novartis, and Pfizer. J.P. reports honoraria for lectures and advisory boards from Novartis, Pfizer, Servier, Orion Pharma and Roche Diagnostics. D.J.v.V. has received board membership fees or travel expenses from Novartis, Johnson & Johnson, and Vifor. M.M. has received personal honoraria for participation in trial committees, advisory boards or speeches at sponsored symposia from Abbott Vascular, Amgen, AstraZeneca, Bayer, Vifor Pharma, Servier, WindTree Therapeutics. F.Z. has received personal fees from Janssen, Novartis, Bayer, Boston Scientific, Amgen, CVRx, Boehringer Ingelheim, AstraZeneca, Vifor Fresenius, Cardior Pharmaceuticals, Cerno Pharmaceuticals, Applied Therapeutics, and Merck; and has received other payments from CVCT and Cardiorenal. D.F. reports speaker honoraria or consultation fees from Abbott Laboratories, Bayer, Boehringer Ingelheim, Menarini, Novartis, Orion Pharma and Roche Diagnostics. A.A.V. received consultancy fees or research grants from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Myokardia, Novartis, Novonordisk, Roche Diagnostics. G.F. reports committee membership in trials and/or registries sponsored by Amgen, Bayer, Novartis, BI, Medtronic, Vifor, Servier. All other authors have nothing to disclose. Funding Information: : V.B. reports honoraria for lectures from AstraZeneca, Novartis, and Pfizer. J.P. reports honoraria for lectures and advisory boards from Novartis, Pfizer, Servier, Orion Pharma and Roche Diagnostics. D.J.v.V. has received board membership fees or travel expenses from Novartis, Johnson & Johnson, and Vifor. M.M. has received personal honoraria for participation in trial committees, advisory boards or speeches at sponsored symposia from Abbott Vascular, Amgen, AstraZeneca, Bayer, Vifor Pharma, Servier, WindTree Therapeutics. F.Z. has received personal fees from Janssen, Novartis, Bayer, Boston Scientific, Amgen, CVRx, Boehringer Ingelheim, AstraZeneca, Vifor Fresenius, Cardior Pharmaceuticals, Cerno Pharmaceuticals, Applied Therapeutics, and Merck; and has received other payments from CVCT and Cardiorenal. D.F. reports speaker honoraria or consultation fees from Abbott Laboratories, Bayer, Boehringer Ingelheim, Menarini, Novartis, Orion Pharma and Roche Diagnostics. A.A.V. received consultancy fees or research grants from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Merck, Myokardia, Novartis, Novonordisk, Roche Diagnostics. G.F. reports committee membership in trials and/or registries sponsored by Amgen, Bayer, Novartis, BI, Medtronic, Vifor, Servier. All other authors have nothing to disclose. Conflict of interest Publisher Copyright: © 2021 European Society of Cardiology. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/7
Y1 - 2021/7
N2 - Background: The role of neurohormonal inhibition in chronic heart failure (HF) is well established. There are limited data on the effect of up-titration of renin–angiotensin inhibitors (RASi) and beta-blockers (BBs) on clinical outcomes of patients with worsening HF across the left ventricular ejection fraction (LVEF) spectrum. Methods and results: We analysed data from 2345 patients from BIOSTAT-CHF (80.9% LVEF <40%), who completed a 3-month up-titration period after recent worsening of HF. Patients were classified by achieved dose (% of recommended): ≥100%, 50–99%, 1–49%, and none. Recurrent event analysis using joint and shared frailty models was used to examine the association between RASi/BB dose and all-cause and HF hospitalizations. In the 21 months following up-titration, 512 patients died and 879 (37.5%) had ≥1 hospitalization. RASi up-titration was associated, incrementally, with reduced risk of all-cause hospitalization at all achieved dose levels compared to no treatment [hazard ratio (95% confidence interval): ≥100%: 0.60 (0.49–0.74), P < 0.001; 50–99%: 0.56 (0.46–0.68), P < 0.001; 1–49%: 0.71 (0.59–0.86), P < 0.001]. This association was consistent up to an LVEF of 49% (P < 0.001), and when considering only HF hospitalizations. Up-titration of BBs was associated with fewer all-cause hospitalizations only when LVEF was <40% (overall P < 0.001), but with more HF hospitalizations when LVEF was ≥50%. Up-titration of both RASi/BBs was associated with lower mortality in LVEF up to 49%. Conclusion: After recent worsening of HF, up-titration of RASi and BBs was associated with a better prognosis in patients with LVEF ≤49%. Up-titration of BBs was associated with a greater risk of HF hospitalization when LVEF was ≥50%.
AB - Background: The role of neurohormonal inhibition in chronic heart failure (HF) is well established. There are limited data on the effect of up-titration of renin–angiotensin inhibitors (RASi) and beta-blockers (BBs) on clinical outcomes of patients with worsening HF across the left ventricular ejection fraction (LVEF) spectrum. Methods and results: We analysed data from 2345 patients from BIOSTAT-CHF (80.9% LVEF <40%), who completed a 3-month up-titration period after recent worsening of HF. Patients were classified by achieved dose (% of recommended): ≥100%, 50–99%, 1–49%, and none. Recurrent event analysis using joint and shared frailty models was used to examine the association between RASi/BB dose and all-cause and HF hospitalizations. In the 21 months following up-titration, 512 patients died and 879 (37.5%) had ≥1 hospitalization. RASi up-titration was associated, incrementally, with reduced risk of all-cause hospitalization at all achieved dose levels compared to no treatment [hazard ratio (95% confidence interval): ≥100%: 0.60 (0.49–0.74), P < 0.001; 50–99%: 0.56 (0.46–0.68), P < 0.001; 1–49%: 0.71 (0.59–0.86), P < 0.001]. This association was consistent up to an LVEF of 49% (P < 0.001), and when considering only HF hospitalizations. Up-titration of BBs was associated with fewer all-cause hospitalizations only when LVEF was <40% (overall P < 0.001), but with more HF hospitalizations when LVEF was ≥50%. Up-titration of both RASi/BBs was associated with lower mortality in LVEF up to 49%. Conclusion: After recent worsening of HF, up-titration of RASi and BBs was associated with a better prognosis in patients with LVEF ≤49%. Up-titration of BBs was associated with a greater risk of HF hospitalization when LVEF was ≥50%.
KW - Beta-blockers
KW - Hospitalizations
KW - Mortality
KW - Renin–angiotensin system inhibitors
KW - Worsening heart failure
UR - http://www.scopus.com/inward/record.url?scp=85107787978&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ejhf.2219
DO - https://doi.org/10.1002/ejhf.2219
M3 - Article
C2 - 33998113
SN - 1388-9842
VL - 23
SP - 1170
EP - 1181
JO - European journal of heart failure
JF - European journal of heart failure
IS - 7
ER -