Nobuhisa Hagiwara    Department   Other, Other    Position
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	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.
Journal	Formal name：European journal of heart failure Abbreviation：Eur J Heart Fail ISSN code：13889842/18790844
Domestic / Foregin	Foregin
Publisher	John Wiley & Sons, Inc.
Volume, Issue, Page	pp.in press
Author and coauthor	Ouwerkerk Wouter, Teng Tiew-Hwa K, Tromp Jasper, Tay Wan Ting, Cleland John G, van Veldhuisen Dirk J, Dickstein Kenneth, Ng Leong L, Lang Chim C, Anker Stefan D, Zannad Faiez, Hung Chung-Lieh, Sawhney Jitendra P S, Naik Ajay, Shimizu Wataru, Hagiwara Nobuhisa, Wander Gurpreet Singh, Anand Inder, Richards A Mark, Voors Adriaan A, Lam Carolyn S P
Publication date	2020/06
Summary	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.
DOI	10.1002/ejhf.1869
PMID	32583922