Abstract

BACKGROUND: Current recommendations for a prophylactic (primary prevention) implantable cardioverter defibrillator (ICD) in patients with both ischemic and nonischemic heart failure with reduced ejection fraction (HFrEF) originate from clinical trials conducted in selected patients over 20 years ago that showed an overall statistically significant survival benefit associated with a primary prevention ICD in the range of 23%-34%. The recent introduction of angiotensin receptor-neprilysin inhibitors [ARNI] and sodium glucose co-transporter 2 inhibitors [SGLT2i]) was shown to further reduce the risk of sudden cardiac death (SCD) in patients with HFrEF. Thus, there is an unmet need appropriately designed comparative effectiveness clinical trials aimed to reassess the survival benefit of a primary prevention ICD in contemporary patients with HFrEF. METHODS: The comparative effectiveness of ICD vs non-ICD therapy in contemporary heart failure patients at a low risk for arrhythmic death (CONTEMP-ICD) trial is a prospective, multicenter, open-label, randomized-controlled trial; enrolling 3,290 participants with HFrEF who are treated with optimal stable GDMT and are eligible for a primary prevention ICD, but have a lower predicted risk of life-threatening ventricular tachyarrhythmia (VTA) than nonarrhythmic mortality. Enrolled participants will be randomized to non-ICD vs ICD treatment arms and will be followed over an average period of 3.5 years. The specific aims of the proposed clinical trial are to: (1) Compare the risk of all-cause mortality of non-ICD vs ICD in HFrEF patients who have a lower predicted risk of VTA than nonarrhythmic mortality per the MADIT-ICD Benefit Score; (2) Evaluate whether non-ICD vs ICD is associated with improved survival free of major CV events in patients with HFrEF who are at a lower predicted arrhythmic risk; (3) Assess healthcare utilization and quality of life implications of non-ICD vs ICD management approaches in HFrEF patients who are at a lower predicted arrhythmic risk; and (4) Determine the effect of non-ICD vs ICD management on all-cause mortality in prespecified subgroups. CONCLUSIONS: We hypothesize that, in patients with HFrEF who are at a lower predicted arrhythmic risk, non-ICD vs ICD is noninferior with respect to the primary endpoint of all-cause mortality and superior with respect to the secondary endpoint of survival free of major CV events. NCT06543446; https://contemp-icd.org.