Background information

Sudden cardiac death is a major unsolved public health problem accounting for ~20% of all deaths in Europe with an estimated yearly incidence of ~350-700,000 cases. These are most frequently patients with previous myocardial infarction (MI). In sudden cardiac death, the heart suddenly and unexpectedly stops beating. If untreated, the patient dies within minutes, but sudden cardiac death can be successfully prevented by a cardiac device, the implantable cardioverter defibrillator (ICD). The ICD is a cardiac device that detects ventricular tachyarrhythmias and terminates them by either rapid ventricular pacing or by the delivery of intracardiac shocks, thereby preventing SCD.  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(Moss et al.) and SCD-HeFT(Bardy et al.), were conducted between end of the 1990s and early 2000s. These trials compared the survival of patients with severely reduced LVEF, either after MI or due to other causes of heart failure, who received a defibrillator with the survival of patients being on medical therapy alone. These two trials 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. Indeed, in these trials and in other studies from this period, therapies delivered by the defibrillators were reported in a substantial portion of patients.

In the meanwhile, there is a whole bulk of evidence that the risk-benefit of defibrillator implantation for primary prevention of SCD in patients with severely reduced LVEF has substantially changed since the conduction of these two landmark trials 20-25 years ago. Existing data are outdated and do no longer represent current therapies, since SCD risk decreased during the last decades as a result of improved patient therapy. A novel randomised adequately powered assessment of the role of the defibrillator under contemporary optimal medical appears imperative.

The ambition of PROFID

The ambition of PROFID is to reassess the role of routine prophylactic ICD implantation in patients with reduced LVEF ≤ 35% after myocardial infarction under contemporary OMT and fundamentally improve clinical practice, potentially resulting in a substantial reduction of the enormous burden that sudden cardiac death places on society as a whole and on the individual patient.

What is the PROFID approach?

PROFID is expected to change SCD prevention in clinical practice. In order to reach the final goal, the following main phases have been designed for the PROFID project:

Data analysis

In the first phase, a variety of data from different settings will be analysed. The analysis will be based on a collection of existing highly phenotyped data with the largest number of post- myocardial infarction patients ever in this regard (~200,000 patients of both sexes).The databases represent a wide variety of data sources such as national registries, institutional research databases, electronic health records and claims databases.

Clinical trial

In the second phase, a non-inferiority randomised clinical trial will compare OMT versus ICD implantation plus OMT in post-MI patients with LVEF ≤ 35% who would receive an ICD according to current clinical guidelines.

Main objective

The ultimate goal is to successfully prevent the majority of the catastrophic sudden cardiac death events that occur after myocardial infarction.

Thus, PROFID aims to close the huge gap of current clinical practice with regard to protection from sudden cardiac death after myocardial infarction.