Effects of combined renin-angiotensin-aldosterone system inhibitor and beta-blocker treatment on outcomes in heart failure with reduced ejection fraction: insights from BIOSTAT-CHF and ASIAN-HF registries

TY - JOUR

T1 - Effects of combined renin-angiotensin-aldosterone system inhibitor and beta-blocker treatment on outcomes in heart failure with reduced ejection fraction

T2 - insights from BIOSTAT-CHF and ASIAN-HF registries

AU - Ouwerkerk, Wouter

AU - Teng, Tiew-Hwa K.

AU - Tromp, Jasper

AU - Tay, Wan Ting

AU - Cleland, John G.

AU - van Veldhuisen, Dirk J.

AU - Dickstein, Kenneth

AU - Ng, Leong L.

AU - Lang, Chim C.

AU - Anker, Stefan D.

AU - Zannad, Faiez

AU - Hung, Chung-Lieh

AU - Sawhney, Jitendra P. S.

AU - Naik, Ajay

AU - Shimizu, Wataru

AU - Hagiwara, Nobuhisa

AU - Wander, Gurpreet Singh

AU - Anand, Inder

AU - Richards, A. Mark

AU - Voors, Adriaan A.

AU - Lam, Carolyn S. P.

N1 - Funding Information Biomedical Research Council Asian neTwork for Translational Research and Cardiovascular Trials (ATTRaCT). Grant Numbers: SPF2014/005, SPF2014/004, SPF2014/003 Boston Scientific Investigator Sponsored Research Program, National Medical Research Council of Singapore. Grant Number: R‐172‐003‐219‐511 European Commission. Grant Numbers: EudraCT 2010‐020808‐29, FP7‐242209‐BIOSTAT‐CHF © 2020 European Society of Cardiology.

PY - 2020/8/1

Y1 - 2020/8/1

N2 - Background: Angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and β-blockers are guideline-recommended first-line therapies in heart failure (HF) with reduced ejection fraction (HFrEF). Previous studies showed that individual drug classes were under-dosed in many parts of Europe and Asia. In this study, we investigated the association of combined up-titration of ACEi/ARBs and β-blockers with all-cause mortality and its combination with hospitalization for HF.Methods and results: A total of 6787 HFrEF patients (mean age 62.6 ± 13.2 years, 77.7% men, mean left ventricular ejection fraction 27.7 ± 7.2%) were enrolled in the prospective multinational European (BIOSTAT-CHF; n = 2100) and Asian (ASIAN-HF; n = 4687) studies. Outcomes were analysed according to achieved percentage of guideline-recommended target doses (GRTD) of combination ACEi/ARB and β-blocker therapy, adjusted for indication bias. Only 14% (n = 981) patients achieved ≥50% GRTD for both ACEi/ARB and β-blocker. The best outcomes were observed in patients who achieved 100% GRTD of both ACEi/ARB and β-blocker [hazard ratio (HR) 0.32, 95% confidence interval (CI) 0.26-0.39 vs. none]. Lower dose of combined therapy was associated with better outcomes than 100% GRTD of either monotherapy. Up-titrating β-blockers was associated with a consistent and greater reduction in hazards of all-cause mortality (HR for 100% GRTD: 0.40, 95% CI 0.25-0.63) than corresponding ACEi/ARB up-titration (HR 0.75, 95% CI 0.53-1.07).Conclusion: This study shows that best outcomes were observed in patients attaining GRTD for both ACEi/ARB and β-blockers, unfortunately this was rarely achieved. Achieving >50% GRTD of both drug classes was associated with better outcome than target dose of monotherapy. Up-titrating β-blockers to target dose was associated with greater mortality reduction than up-titrating ACEi/ARB.

AB - Background: Angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and β-blockers are guideline-recommended first-line therapies in heart failure (HF) with reduced ejection fraction (HFrEF). Previous studies showed that individual drug classes were under-dosed in many parts of Europe and Asia. In this study, we investigated the association of combined up-titration of ACEi/ARBs and β-blockers with all-cause mortality and its combination with hospitalization for HF.Methods and results: A total of 6787 HFrEF patients (mean age 62.6 ± 13.2 years, 77.7% men, mean left ventricular ejection fraction 27.7 ± 7.2%) were enrolled in the prospective multinational European (BIOSTAT-CHF; n = 2100) and Asian (ASIAN-HF; n = 4687) studies. Outcomes were analysed according to achieved percentage of guideline-recommended target doses (GRTD) of combination ACEi/ARB and β-blocker therapy, adjusted for indication bias. Only 14% (n = 981) patients achieved ≥50% GRTD for both ACEi/ARB and β-blocker. The best outcomes were observed in patients who achieved 100% GRTD of both ACEi/ARB and β-blocker [hazard ratio (HR) 0.32, 95% confidence interval (CI) 0.26-0.39 vs. none]. Lower dose of combined therapy was associated with better outcomes than 100% GRTD of either monotherapy. Up-titrating β-blockers was associated with a consistent and greater reduction in hazards of all-cause mortality (HR for 100% GRTD: 0.40, 95% CI 0.25-0.63) than corresponding ACEi/ARB up-titration (HR 0.75, 95% CI 0.53-1.07).Conclusion: This study shows that best outcomes were observed in patients attaining GRTD for both ACEi/ARB and β-blockers, unfortunately this was rarely achieved. Achieving >50% GRTD of both drug classes was associated with better outcome than target dose of monotherapy. Up-titrating β-blockers to target dose was associated with greater mortality reduction than up-titrating ACEi/ARB.

KW - Evidence-based pharmacotherapy

KW - Heart failure

KW - Outcomes

KW - Reduced ejection fraction

KW - Up-titration

UR - https://www.scopus.com/pages/publications/85087178957

U2 - 10.1002/ejhf.1869

DO - 10.1002/ejhf.1869

M3 - Article

C2 - 32583922

SN - 1388-9842

VL - 22

SP - 1472

EP - 1482

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

IS - 8

ER -