Sudden Cardiac Death, Myocardial Infarction
Conditions
Keywords
Implantable Cardioverter Defibrillator, Sudden Cardiac Death, Myocardial Infarction
Brief summary
Patients who have survived a myocardial infarction (MI) are at increased risk for sudden cardiac death (SCD) caused by ventricular tachycardia and ventricular fibrillation. A severely reduced left ventricular ejection fraction (LVEF) as a rough overall measure of impaired heart function after MI was shown to indicate a higher risk for SCD. Based on this observation, two landmark randomised trials, MADIT II and SCD-HeFT, were conducted between end of the 1990s and early 2000s. These trials compared the survival of patients with severely reduced LVEF who received an implantable cardioverter-defibrillator with the survival of patients being on medical therapy alone. They reported a significantly better survival of patients in the defibrillator arm and led to international guideline recommendations for routine implantation of defibrillators in survivors of MI with severely impaired LVEF as a means for primary prevention of SCD. Since then, the management of these patients has changed dramatically with the advent of a series of novel drug classes that reduce not only mortality but specifically SCD leading to a substantial decrease of the sudden death rates as well as of the rates of appropriate defibrillator therapies implanted for primary prevention of SCD. At the same time, the complication rates associated with the defibrilllator therapy remain significant without obvious decrease. Thus, the risk-benefit of routine defibrillator implantation for primary prevention of SCD in patients with severely reduced LVEF has substantially changed since the conduction of the landmark trials that established this therapy. Due to the inherent risks and considerable costs of the defibrillator, a novel randomised adequately powered assessment of the potential benefit or harm of the defibrillator in survivors of MI with reduced LVEF under contemporary optimal medical treatment (OMT) appears imperative. OBJECTIVE: To demonstrate that in post-MI patients with symptomatic heart failure who receive OMT for this condition, and with reduced LVEF ≤ 35%, OMT without ICD implantation (index group) is not inferior to OMT with ICD implantation (control group) with respect to all-cause mortality.
Interventions
A transvenous ICD consists of an electronic medical device and electrode leads. Besides the possibility to shock during arrhythmias the ICD can potentially terminate ventricular tachycardias by rapid pacing for short periods (small bursts of pacing). The subcutaneous defibrillator is an established and valid alternative to the transvenous ICD for the prevention of SCD, but in patients without an indication for bradycardia support, cardiac resynchronisation or antitachycardia pacing. The extravascular implantable cardioverter-defibrillator (EV ICD) system with substernal lead placement is a novel nontransvenous alternative to current available transvenous and subcutaneous ICDs.
Patients will be treated according to Optimal Medical Therapy defined by the following guidelines: 1. 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes 2. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure
Sponsors
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Masking description
The PROFID EHRA trial is an open-label, blinded outcome assessment study. Thus, unblinding procedures for investigators are not applicable.
Intervention model description
An investigator-driven, prospective, parallel-group, randomised, open, blinded outcome assessment (PROBE), multi-centre, non-inferiority trial without investigational medical products (Proof of Strategy Trial)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years. 2. Naïve to implantation of any pacemaker or defibrillator 3. Documented history of MI either as ST segment elevation myocardial infarction (STEMI) or as non-ST segment elevation myocardial infarction (NSTEMI) at least 3 months prior to enrolment. 4. Symptomatic heart failure with New York Heart Association (NYHA) class II or III. 5. On OMT for at least 3 months prior to enrolment. 6. LVEF ≤ 35% (at transthoracic echocardiography or cardiac magnetic resonance imaging \[MRI\] at least 3 months after MI). 7. Signed informed consent. Inclusion criterion I3 defines myocardial infarction according to the 2018 ESC/ACC/AHA/WHF Fourth Universal Definition of myocardial infarction
Exclusion criteria
1. Class I or IIa indication for implantation of an ICD for secondary prevention of SCD and ventricular tachycardia. 2. Ventricular tachycardia induced in an electrophysiologic study. 3. Unexplained syncope when ventricular arrhythmia is suspected as the cause of syncope. 4. Class I or IIa indication for Cardiac Resynchronization Therapy (CRT) 5. Foreseable violation of instruction for use (IFU) of the ICD device selected for implantation (valid for control group patients, only). 6. Acute coronary syndrome or coronary angioplasty or coronary artery bypass grafting performed within 6 weeks prior to enrolment. 7. Cardiac valve surgery or percutaneous cardiac valvular intervention performed within 6 weeks prior to enrolment. 8. On the waiting list for heart transplantation. Class I or IIa indication for implantation of an ICD for secondary prevention of SCD and ventricular tachy-cardia has to be assessed according to the 2022 ESC Guidelines for the management of patients with ven-tricular arrhythmias and the prevention of SCD. 9. Any known disease that limits life expectancy to less than 1 year. 10. Participation in another randomised clinical trial if study-specific treatment is still active at enrolment into PROFID EHRA. 11. Previous participation in PROFID EHRA. Parallel participation in sub-studies connected to this trial is permitted as well as in purely observational studies without any pre-defined intervention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time from randomisation to the occurrence of all-cause death. | event-driven, expected about 15 months after last patient in | Randomization to end of study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time from randomisation to death from cardiovascular causes | Randomization to end of study (event-driven, expected about 15 months after last patient in | Time from randomisation to death from cardiovascular causes |
| Time from randomisation to sudden cardiac death | Randomization to end of study (event-driven, expected about 15 months after last patient in | Time from randomisation to sudden cardiac death |
| Time from randomisation to first hospital readmissions for cardiovascular causes after date of randomisation | Randomization to end of study (event-driven, expected about 15 months after last patient in | Time from randomisation to first hospital readmissions for cardiovascular causes after date of randomisation |
| Average length of stay in hospital during the study period | Randomization to end of study (event-driven, expected about 15 months after last patient in | Average length of stay in hospital during the study period |
| Quality of life (EQ-5D-5L) trajectories over time | At baseline and 12-month intervals thereafter | Quality of life (EQ-5D-5L) trajectories over time |
Countries
Austria, Belgium, Czechia, Denmark, France, Germany, Hungary, Israel, Martinique, Netherlands, Poland, Spain, United Kingdom
Contacts
CONTACTGerhard Hindricks, Prof
CONTACTNikolaos Dagres, MD
PRINCIPAL_INVESTIGATORGerhard Hindricks, Prof
Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine
PRINCIPAL_INVESTIGATORNikolaos Dagres, MD
Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine
Outcome results
None listed