MANCHESTER — A large UK multicentre randomised trial is underway to find out whether or not implantable cardioverter defibrillators (ICDs) could reduce the risk of sudden cardiac death in patients with nonischaemic cardiomyopathy.
"The reason that we're doing it is because there was a large study called DANISH [Danish ICD Study in Patients With Dilated Cardiomyopathy] that showed that, on the whole, this group of patients doesn't benefit from ICDs," Dr Andrew Flett, who is one of the study's two main coordinators , told Medscape News UK.
"The concern is that there could be a subgroup that wasn't well represented in DANISH, that could still be at risk of events – so sudden death, predominantly," added Dr Flett, who is a consultant cardiologist at University Hospital Southampton (UHS) NHS Trust .
The BRITISH trial will look at the subgroup of patients that have scar tissue in the left ventricle seen on cardiac magnetic resonance (CMR) imaging and if they benefit from an ICD.
"We think scar could be a risk marker for sudden death", said Dr Flett. "We don't know if that risk is enough to justify having an ICD, particularly with modern day therapy, because all the most recent heart failure drugs have dramatically reduced the risk of sudden death overall".
While the absolute risk for sudden death in these patients might be small, this is not a small group of patients. Non-ischaemic cardiomyopathy accounts for at least half of all heart failure patients, and of those, 40% have scar.
Recruitment 'On Track'
Recruitment into the BRITISH [Using Cardiovascular Magnetic Resonance Identified Scar as the Benchmark Risk Indication Tool for Implantable Cardioverter Defibrillators in Patients with Non-Ischaemic Cardiomyopathy and Severe Systolic Heart Failure] study is "on track", according to Dr Flett.
So far, 5 of a planned 35 recruiting centres are open and 10 patients have been recruited into the study. A pilot phase will run first, aiming to get all centres open and at least 228 (~90%) of an initial 256 patients enrolled within the year. The latter is critical for the trial to be able to continue and keep it's £1.8 million of funding from the British Heart Foundation.
The ultimate goal to get 1252 patients into the prospective study and another 1252 into an accompanying observation registry within 3 years, Dr Flett explained. All patients will undergo CMR imaging and those with scar will enter the trial and those without can enter the observational registry.
For inclusion in the trial patients will need to be over the age of 18 and have severely impaired (≤35%) left ventricular function (LVEF) despite receiving optimal medical therapy for at least 3 months. Patients will be randomised 1:1 to ICD or no ICD, with the latter group receiving optimal medical therapy and an implantable loop recorder (ILR). Patients will be followed up for 3 years for the primary endpoint of all-cause mortality, with further follow up at 5 and 10 years. Other endpoints will include patient wellbeing, sudden cardiac deaths, 'shocks', arrhythmia, and the need for hospitalisation.
Some Clinicians Cautious
The BHF's medical director, Professor Sir Nilesh Samani, commented in a press statement: "ICDs are crucial devices to treat sudden cardiac arrest and save lives. But it is important that we continue to establish exactly which patients need them, so that people who are unlikely to benefit do not have to undergo invasive procedures unnecessarily."
Dr Flett said: "The hypothesis is that scar patients will benefit", noting that new guidance from the European Society for Cardiology suggest that everyone should be getting a CMR scan anyway, so there would not be any additional cost involved for imaging.
Upon hearing the findings at the BCS conference, some clinicians seemed cautious on the inclusion criteria and definition of scar being used.
"My concern is about selection bias," consultant cardiologist Dr Zachary Whinnet of Imperial College London, told Medscape Medical News. "The difficulty is that you may recruit sicker patients and put them into the study." Those patients, he added, may be older and have other competing risk factors, while younger patients with fewer competing risks might be excluded.
The danger is that the trial will show non-inferiority and might lead to guideline changes that make it more difficult to implant ICDs in younger patients who are at high risk for sudden cardiac death, Dr Whinnet suggested. "[The investigators] are probably aware of that. But it's very difficult," he said.
Also somewhat reserved was consultant cardiologist Dr Francis Murgatroyd, who works at Kings College Hospital in London. The potential problem he saw was in the binary definition of scar.
"If we really try to, we can convince ourselves of a little bit of scar in a lot of patients, and there's a huge difference between a couple of little white flecks of scar and very dense scar," Dr Murgatroyd said.
"Clearly the amount of scar, the distribution, everyone believes is actually an indicator of risk. But [the investigators] are saying there is none at all or any scar. But I'm sure post hoc, they'll be looking at that".
The study is being supported by the British Heart Foundation. No conflicts of interest were reported by any of the people that were interviewed.