Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial

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Title: Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial
Authors: Halliday, BP
Wassall, R
Lota, A
Khalique, Z
Gregson, J
Newsome, S
Jackson, R
Rahneva, T
Wage, R
Smith, G
Venneri, L
Tayal, U
Auger, D
Midwinter, W
Whiffin, N
Rajani, R
Dungu, J
Cook, S
Ware, J
Baksi, J
Pennell, D
Rosen, S
Cowie, M
Cleland, J
Prasad, S
Item Type: Journal Article
Abstract: Background Patients with dilated cardiomyopathy whose symptoms and cardiac function have recovered often ask whether their medications can be stopped. The safety of withdrawing treatment in this situation is unknown. Methods We did an open-label, pilot, randomised trial to examine the effect of phased withdrawal of heart failure medications in patients with previous dilated cardiomyopathy who were now asymptomatic, whose left ventricular ejection fraction (LVEF) had improved from less than 40% to 50% or greater, whose left ventricular end-diastolic volume (LVEDV) had normalised, and who had an N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) concentration less than 250 ng/L. Patients were recruited from a network of hospitals in the UK, assessed at one centre (Royal Brompton and Harefield NHS Foundation Trust, London, UK), and randomly assigned (1:1) to phased withdrawal or continuation of treatment. After 6 months, patients in the continued treatment group had treatment withdrawn by the same method. The primary endpoint was a relapse of dilated cardiomyopathy within 6 months, defined by a reduction in LVEF of more than 10% and to less than 50%, an increase in LVEDV by more than 10% and to higher than the normal range, a two-fold rise in NT-pro-BNP concentration and to more than 400 ng/L, or clinical evidence of heart failure, at which point treatments were re-established. The primary analysis was by intention to treat. This trial is registered with, number NCT02859311. Findings Between April 21, 2016, and Aug 22, 2017, 51 patients were enrolled. 25 were randomly assigned to the treatment withdrawal group and 26 to continue treatment. Over the first 6 months, 11 (44%) patients randomly assigned to treatment withdrawal met the primary endpoint of relapse compared with none of those assigned to continue treatment (Kaplan-Meier estimate of event rate 45·7% [95% CI 28·5–67·2]; p=0·0001). After 6 months, 25 (96%) of 26 patients assigned initially to continue treatment attempted its withdrawal. During the following 6 months, nine patients met the primary endpoint of relapse (Kaplan-Meier estimate of event rate 36·0% [95% CI 20·6–57·8]). No deaths were reported in either group and three serious adverse events were reported in the treatment withdrawal group: hospital admissions for non-cardiac chest pain, sepsis, and an elective procedure. Interpretation Many patients deemed to have recovered from dilated cardiomyopathy will relapse following treatment withdrawal. Until robust predictors of relapse are defined, treatment should continue indefinitely.
Issue Date: 5-Jan-2019
Date of Acceptance: 3-Oct-2018
ISSN: 0140-6736
Publisher: Elsevier
Start Page: 61
End Page: 73
Journal / Book Title: The Lancet
Volume: 393
Issue: 10166
Copyright Statement: © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license (
Sponsor/Funder: Wellcome Trust
British Heart Foundation
Funder's Grant Number: 107469/Z/15/Z
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
Cardiomyopathy, Dilated
Cardiovascular Agents
Drug Administration Schedule
Heart Failure
Kaplan-Meier Estimate
Middle Aged
Natriuretic Peptide, Brain
Peptide Fragments
Pilot Projects
Remission Induction
Stroke Volume
Treatment Outcome
Ventricular Function, Left
Withholding Treatment
11 Medical And Health Sciences
Publication Status: Published
Online Publication Date: 2018-11-11
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine

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