Therapy withdrawal in REcovered Dilated cardiomyopathy trial (TRED)
Research type
Research Study
Full title
A randomised controlled pilot trial of the feasibility and safety of therapy withdrawal in asymptomatic patients with a prior diagnosis of dilated cardiomyopathy & recovered cardiac function.
IRAS ID
171308
Contact name
Sanjay Prasad
Contact email
Sponsor organisation
Royal Brompton & Harefield NHS Foundation Trust
Eudract number
2015-005351-27
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Summary of Research
Dilated cardiomyopathy (DCM) is the most common disease of the heart muscle. It is characterised by a reduction in function and increase in size of the heart’s pumping chambers. In 1 in 3 patients, the heart function improves with heart medications; these patients have an excellent long-term prognosis. A question we are often asked by patients is whether they need to continue medications after their heart function has completely recovered. It is unclear whether patients continue to derive benefit from medications or whether these should be stopped. Practice amongst doctors currently varies and no recommendations are made in international practice guidelines.In this randomised controlled pilot study we will investigate whether it is safe and feasible for patients with DCM, recovered heart function and no symptoms of heart failure to stop their heart medications.
We will study 50 patients with DCM who have recovered heart function and no symptoms of heart failure. We will randomly assign them to either continue their heart medications or stop them in a gradual, closely supervised fashion. We will monitor patients over 6 months using cardiac-sensitive blood tests, exercise tests and heart MRI scans. Patients will be reviewed by doctors every 2 weeks while they stop their medications and these will be restarted if there is any worsening of their condition. At 6 months we will compare the groups and determine whether it was safe and feasible to stop medications.
If it is safe, we will go on to perform a larger study looking at the impact of withdrawing medications in the long-term. This work aims to answer a question that is important to both patients and doctors.
Summary of Results
Dilated cardiomyopathy (DCM) is a disease where the heart muscle becomes 'dilated', or stretched. As a result, the heart becomes weak, thin or floppy, which can lead to heart failure. In many people with DCM and heart failure, heart function improves with treatment. And in some people, symptoms can resolve completely.Many patients without symptoms of heart failure want to know whether they still need lifelong treatment, especially if they are experiencing side-effects. These patients are often young, can be taking up to four different types of drug every day, and face 40 to 50 years of treatment. In particular, young women are often keen to stop treatment before trying to become pregnant.
However, there was no evidence showing that stopping heart failure treatment in this situation is safe, or if this would lead to symptoms returning. The ‘Therapy withdrawal in REcovered Dilated cardiomyopathy – Heart Failure’ (TRED-HF) trial led by Dr Sanjay Prasad at the Royal Brompton Hospital, Imperial College London, and funded by the BHF, was conducted to help address this important clinical dilemma.
What did the study involve?
From 2016 to 2018, the TRED-HF trial recruited and followed up 51 people with DCM. Participants had recovered heart function and no symptoms. All were still on heart failure medications when they joined the study. They were randomly assigned to either:- Phased stopping or ‘withdrawal’ of their medication. The withdrawal was done gradually over 16 weeks. The trial team reduced the dose of one drug every 2 weeks until it was completely stopped, and then reduced the next drug/s in the same way.
- Continuation of treatment. After 6 months, patients in the ‘continued treatment’ group also had their treatment withdrawn.The researchers made sure that all participants were closely monitored to minimise any risks to their health. They discussed the possible risk of recurrence of heart failure and irregular heart rhythms on withdrawal of treatment with all participants. And they kept in close contact - with regular telephone interviews and clinic assessments (involving blood tests, exercise tests and heart MRI scans). Serious events were quickly reported, and the team restarted medical treatment immediately if any participant’s condition worsened.
What did the study show?
Over the first 6 months, 11 of 25 participants (44%) who stopped their medication relapsed.
No relapse was seen in people who kept taking their treatment.
After 6 months, people in the continued treatment group also had treatment withdrawn. In this group, 9 of 25 (36%) relapsed.
Altogether, only 16 participants out of 50 were was deemed to have 'successful' withdrawal of therapy.
The researchers recommended that heart failure treatment was restarted in all participants at the end of the trial, even in the 16 people with successful withdrawal. This was due to the risk of relapse in the long-term. There were no deaths or unplanned hospitalisations. At the next follow-up after restarting treatment, none of the ‘relapsed patients’ had symptoms of heart failure, and 85% had completely recovered heart function.Why is the study important?
This trial showed for the first time that it is not advisable to withdraw heart failure medication in many people with DCM, even if they are asymptomatic.Although the findings of the trial were disappointing to people with DCM and doctors, the results of TRED-HF provoked much interest among cardiologists. This study provided invaluable evidence to back-up long term prescription of medication in people with DCM, even if their heart failure seems to have recovered.
REC name
London - Surrey Borders Research Ethics Committee
REC reference
16/LO/0065
Date of REC Opinion
17 Feb 2016
REC opinion
Further Information Favourable Opinion