Cardioverter DefIbriIlator PlacEMent for priMary Prevention of Sudden cArdiac Death in Patients Older Than 75 Years (DILEMMA)

Cardioverter DefIbriIlator PlacEMent for priMary Prevention of Sudden cArdiac Death in Patients Older Than 75 Years

Cardioverter DefIbriIlator PlacEMent for priMary Prevention of Sudden cArdiac Death in Patients Older Than 75 Years: A Randomized Controlled Trial

The primary objective of DILEMMA study is to assess whether the "heart failure optimal therapy alone (HFOT)" strategy is non inferior to the "HFOT+ICD" strategy in terms of overall survival 48 months after randomization, in patients ≥ 75 years with an ICD indication for primary prevention of SCD whether there is an indication for cardiac resynchronization therapy or not.

Rationale Although not recognized by guidelines, there is no available data demonstrating the benefit of Implantable Cardioverter Defibrillator (ICD) for primary prevention strategy of Sudden Cardiac Death (SCD) in elderly. Nevertheless, ICD are currently implanted in this population by extending the results obtained in randomized trials involving younger subjects to the elderly. Finally, if the absence of implantation in the elderly was not inferior to the implantation of such a device, the non-implantation would avoid the device-related complications and decrease the health costs. Main objective The primary objective of DILEMMA study is to assess whether the "heart failure optimal therapy alone (HFOT)" strategy is non inferior to the "HFOT+ICD" strategy in terms of overall survival 48 months after randomization, in patients ≥ 75 years with an ICD indication for primary prevention of SCD whether there is an indication for cardiac resynchronization therapy or not. Design This is a 2-arm parallel non-inferiority, randomized, open label, multicenter trial. 730 patients will be included over 4 years. Follow up will last 4 years.

Heart Failure, Prevention strategy of Sudden Cardiac Death, Implantable cardioverter defibrillator, Heart Failure Optimal Therapy, Mortality

Three experts in cardiac electrophysiology and ICD will be in charge of uniformly approving, while blinded to the study group, ICD tracings, cardiovascular events, including specific causes of death, in order to validate the primary and secondary endpoints.

Heart failure Optimal therapy without implantable cardioverter defibrillator. This group will not undergo an ICD implantation. They will be treated according to the HFOT recommended in the latest guidelines.

Optimal medical therapy + implantable cardioverter defibrillator (HFOT+ICD). This group will undergo an ICD implantation (standard of care), any brand, CE marked, implantable (lifelong), available and reimbursed in the French market (the type and manufacturer at the discretion of the local investigator) in addition to heart failure medical therapy optimization.

This group will undergo an ICD implantation (type and manufacturer at the discretion of the local investigator) in addition to heart failure medical therapy optimization. Patients of the "HFOT+ICD" group will be scheduled for ICD implantation.

Patients of the "HFOT alone" group will not undergo ICD implantation (except if they develop sustained ventricular arrhythmias and fulfil for secondary prevention ICD implantation), and continue with medical therapy optimization only.

The primary endpoint will be the overall survival at 48 months after randomization to "HFOT alone" group or "HFOT+ICD" group. There is an annual follow-up with precise date of the fatal event and specific cause of death adjudicated by the blinded event committee.

Rate of sudden cardiac death and rate of death from ventricular arrhythmias assessed by a blinded endpoint committee.

Number of ICD related therapies (antitachycardia pacing and shocks), hematoma, infection related to the device, lead dislodgement requiring intervention, pneumothorax and tamponade.

Global quality of life score with SF36 (Short form 36 health survey) : the norm data is 0-100, the health related quality of life is increased as the scores are increased.

Health-related quality of life measured by using the European Quality Of Life (EQ-5D) auto-questionnaire. The digits for the five dimensions are combined into a 5-digit number that describes the patient's health state. The visual analogue scale (VAS) records the patient's self-rated health on a vertical axis from 0 (worst health) to 100 (best health)

The Minnesota Living with Heart Failure will be used to measure the subjects perception of how their heart failure affect their life. Norm data is 0-105 (21 items ; score 0-5), quality of life increases as scores decrease.

The ICUR is calculated by dividing the difference between the average costs of both groups by the difference in mean QALYs gained in both groups. The QALYs will be constructed with the EuroQoL-5D (EQ-5D) questionnaire and value sets.

The ICER will estimate the cost per additional survivor and is calculated by dividing the difference between the average costs of both groups by the difference in effectiveness (survival) between both groups.

Inclusion Criteria: ≥75 years old, Left ventricular ejection fraction ≤ 35% NYHA class II or III Heart failure HFOT ≥ 3 months Providing informed consent Affiliated to a French Health Insurance system. Exclusion Criteria: Enrolled in or planning to enroll in a conflicting interventional trial Prior unstable sustained ventricular arrhythmia requiring external cardioversion Myocardial infarction within the 40 days Coronary artery intervention (catheter or surgical) within 90 days History of syncope in the previous 6 months Advanced cerebrovascular disease Cognitive impairment leading to the incapacity of consent Any disease other than cardiac disease (e.g. cancer, uremia, liver failure), associated with a likelihood of survival less than 1 year. Patient under tutorship, curatorship, or legal safeguard Persons deprived of their liberty by judicial or administrative decision (prisoner)

Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared

Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered. Data sharing must respect the agreements made with funders. Teams wishing obtain IPD must meet the sponsor and PI team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasability and financial support will be discussed before mandatory contractual agreement. Processing of shared data must comply with European General Data Protection Regulation (GDPR).