Heart failure - TRED-HF

The clinical question

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 After 6 months, patients in the ‘continued treatment’ group also had their treatment withdrawn.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.

Dr Brian Halliday, who presented the results of TRED-HF at the 2018 American Heart Association meeting in Chicago, explained that the trial had shown that: “Improvement in function represents remission rather than permanent recovery for many patients.”

The participant voice

But what was it like to take part in the trial? You can read about Mike and Jane's experience participating in TRED-HF on the BHF blog. 

Study details

"Is it safe to withdraw medical therapy from patients with a previous diagnosis of dilated cardiomyopathy, now in remission?"
Award reference:  FS/15/29/31492
Principal Investigator: Dr Sanjay Prasad, Imperial College London
Trial registration number: NCT02859311

Publication details

Halliday BP, Wassall R, Lota AS, et al. Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. Lancet. 2019;393(10166):61-73.