Accelerated and personalized therapy for heart failure with reduced ejection fraction

Shen, L. et al. (2022) Accelerated and personalized therapy for heart failure with reduced ejection fraction. European Heart Journal, 43(27), pp. 2573-2587. (doi: 10.1093/eurheartj/ehac210) (PMID:35467706)

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Previously, guidelines recommended initiating therapy in patients with heart failure and reduced ejection fraction (HFrEF) in a sequence that follows the chronological order in which trials were conducted, with cautious up-titration of each treatment. It remains unclear whether this historical approach is optimal and alternative approaches may improve patient outcomes. The potential reductions in events that might result from (i) more rapid up-titration of therapies used in the conventional order (based on the chronology of the trials), and (ii) accelerated up-titration and using treatments in different orders than is conventional were modelled using data from six pivotal trials in HFrEF. Over the first 12 months from starting therapy, using a rapid up-titration schedule led to 23 fewer patients per 1000 patients experiencing the composite of heart failure hospitalization or cardiovascular death and seven fewer deaths from any cause. In addition to accelerating up-titration of treatments, optimized alternative ordering of the drugs used resulted in a further reduction of 24 patients experiencing the composite outcome and six fewer deaths at 12 months. The optimal alternative sequences included sodium-glucose cotransporter 2 inhibition and a mineralocorticoid receptor antagonist as the first two therapies. Modelling of accelerated up-titration schedule and optimized ordering of treatment suggested that at least 14 deaths and 47 patients experiencing the composite outcome per 1000 treated might be prevented over the first 12 months after starting therapy. Standard treatment guidance may not lead to the best patient outcomes in HFrEF, though these findings should be tested in clinical trials.

Item Type:Articles
Additional Information:This work was supported by the National Natural Science Foundation of China (82100404 to L.S.), the British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217 to J.J.V.M. and M.C.P.).
Keywords:Treatment, heart failure, pharmacology, hospitalization, mortality.
Glasgow Author(s) Enlighten ID:Docherty, Dr Kieran and Shen, Dr Li and Jhund, Professor Pardeep and McMurray, Professor John and Petrie, Professor Mark
Authors: Shen, L., Jhund, P. S., Docherty, K. F., Vaduganathan, M., Petrie, M. C., Desai, A. S., Køber, L., Schou, M., Packer, M., Solomon, S. D., Zhang, X., and McMurray, J. J. V.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:European Heart Journal
Publisher:Oxford University Press
ISSN (Online):1522-9645
Published Online:25 April 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in European Heart Journal 43(27): 2573-2587
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science