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. 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. The implantable cardioverter defibrillator is highly effective, but is also associated with potentially severe complications and high health care costs. Based on evidence from older (and outdated) landmark trials, current guidelines recommend prophylactic implantable cardioverter defibrillator implantation in post-myocardial infarction patients with left ventricular ejection fraction (LVEF)≤35% to prevent sudden cardiac death. However, in only a minority will the implantable cardioverter defibrillator ever deliver a lifesaving therapy. Moreover, in absolute numbers the majority of cases of sudden cardiac death occur in patients with a LVEF>35%, currently not considered for prophylactic implantable cardioverter defibrillator. Due to the devastating consequences of sudden cardiac death and the considerable health care expenditures associated with implantable cardioverter defibrillator therapy, a personalised treatment approach for prediction of sudden cardiac death and prevention by implantable cardioverter defibrillator implantation is urgently required. > > Lay Summary

The ambition of PROFID is to introduce a disruptive innovation in the prevention of sudden cardiac death in post- myocardial infarction patients by introducing – for the first time – a personalised treatment approach. PROFID aims at transforming and fundamentally improving clinical practice in this clinically high relevant field of cardiology from a “one-size-fits-all” to “individualised” treatment strategy, 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. > Lay Summary

In order to reach the final goal, the following main phases have been designed for the PROFID project:

Clinical prediction model development
In the first phase, a variety of data from different settings will be included in order to develop a clinical prediction model for the individual risk of sudden cardiac death. This model 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 trials
In the second phase, two parallel randomised clinical trials will validate the utility of use of the clinical prediction model for the decision making on implantable cardioverter defibrillator implantation, while health economic analyses will assess its economic impact on health care systems. Both studies are prospective, parallel-group, randomised, open-label, multi-centre, blinded outcome assessment (PROBE), event-driven trials.

• Trial 1: PROFID-Reduced Non-inferiority trial in reduced LVEF and low sudden cardiac death risk
  Non-inferiority controlled clinical trial without investigational product (Proof of Strategy Trial). This trial will be conducted on about 2,500 patients with a LVEF≤35% and a low risk for sudden cardiac death as predicted by the clinical prediction model that would receive an ICD according to current guidelines with randomised comparison of the ICD versus just optimal medical treatment without ICD.
• Trial 2: PROFID-Preserved Superiority trial in preserved or moderately reduced LVEF and high sudden cardiac death risk
  Superiority controlled clinical trial without investigational product (Proof of Strategy Trial). This trial (“PROFID-Preserved”) will be conducted on more than 1,400 patients with a LVEF>35% and a high risk for sudden cardiac death as predicted by the clinical prediction model that would not receive an ICD according to current guidelines with randomised comparison of the ICD versus just optimal medical treatment without ICD.

Online web-based tool
A software tool for clinical use of the risk score will be implemented and hosted at the website of the European Society of Cardiology. The unique composition of the PROFID consortium with participation of key opinion leaders, patient organisations, large hospital chains, payers, policy makers and state authorities across Europe, will ensure implementation into routine clinical practice. > Lay Summary

For more information about the methodology of this project, please click here.

The aim of PROFID is to develop a personalized prediction of risk for sudden cardiac death after myocardial infarction, a leading cause of death in Europe, as well as a personalized sudden cardiac death prevention by targeted implantation of an implantable cardioverter-defibrillator. The ultimate goal is to successfully prevent the majority of the catastrophic sudden cardiac death events that occur after myocardial infarction by accurate and timely identification of those patients that are at high risk for sudden cardiac death (based on multiple factors, over and above LVEF, including relevant clinical characteristics/biomarkers) followed by implantable cardioverter defibrillator implantation. Thus, PROFID aims to close the huge gap of current clinical practice with regard to protection from sudden cardiac death after myocardial infarction.> Lay Summary