While younger patients appeared to benefit, implantable cardioverter-defibrillators (ICDs) did not improve the primary endpoint overall in the CMR GUIDE trial, according to new data presented at the European Society of Cardiology (ESC) congress (28–31 August, Munich, Germany) and published simultaneously in the Journal of the American Medical Association (JAMA).
ICDs are currently recommended to prevent sudden cardiac death in certain patients with heart failure—namely those with left ventricular ejection fraction (LVEF) that is substantially reduced to 35% or less, despite optimised heart failure medication. However, as noted by CMR GUIDE principal investigator Joseph Selvanayagam (Flinders University, Adelaide, Australia), most sudden cardiac deaths occur in patients with mild-to-moderate LVEF reductions who are not currently eligible for an ICD for primary prevention.
“In the CMR GUIDE trial, we assessed whether an ICD could improve outcomes in patients with LVEF 36–50% who have evidence of myocardial scarring—a risk factor for sudden cardiac death,” Selvanayagam added.
The trial was conducted at 18 centres in Australia, Germany and the UK. A total of 353 patients with ischaemic or non-ischaemic cardiomyopathy, LVEF 36–50% on optimal heart failure therapy and myocardial scarring confirmed by cardiovascular magnetic resonance imaging (MRI) were included. They were randomised 1:1 to receive an ICD or an implantable loop recorder (ILR), which monitors heart rate only. Some 68% of participants were older than 70 years of age and 18% were women.
The primary endpoint of sudden cardiac death or haemodynamically significant ventricular arrhythmias—ventricular arrhythmias producing loss of consciousness or significant drop in blood pressure—was not significantly different between an ICD or an ILR. The primary endpoint occurred in 7.8% of patients assigned to ICDs and 9.2% assigned to ILRs (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.37–1.58). In a prespecified subgroup analysis, ICD implantation was associated with a 72% reduction in the primary endpoint in patients younger than 70 years, whereas no benefit was observed in patients aged 70 years or older.
Additionally, the secondary endpoint of sudden cardiac death was significantly reduced in the ICD group compared with the ILR group (1.7% vs 5.8%; HR, 0.26; 95% CI, 0.07–0.95).
“Overall, the primary endpoint was neutral,” Selvanayagam commented. “However, younger patients appeared to derive clinical benefit from ICDs. We suggest that data from the CMR GUIDE trial are discussed with younger patients in whom ICDs may be an option in a shared decision-making process.”
Finally, Selvanayagam remarked that data and insights from CMR GUIDE could be used to inform future trials in a larger number of patients.
