CoroPrevention

Coronary heart disease (CHD) remains the leading cause of premature death worldwide. CHD affects both men and women and of all deaths before the age of 75 years in Europe, 42% in women and 38% in men are due to CHD. Thus, prevention of CHD morbidity and mortality is a major challenge in clinical medicine. Cardiovascular diseases cost the EU economy almost €294 billion a year, and are projected to rise with both the ageing population and the cost of
novel treatments.

European and global CHD burden remains unsustainable. Better risk stratification tools and personalized care of patients are needed for reducing morbidity and mortality of CHD and the associated economic burden. To this end we present here a plan to shape and implement a personalized secondary prevention strategy for patients with established CHD. This precision strategy will be tested in a prospective trial, the CoroPrevention Trial, a central element of our ambitious proposal.

Given the high prevalence of CHD, the prevention of morbidity and mortality in patients with established CHD is a major public health objective and the focus of this project. We aim to significantly reduce the numbers of coronary events, namely, myocardial infarctions (MI) and coronary deaths by using outcome risk- and patient characteristicsguided prevention in CHD patients. Since majority of CHD patients remain stable throughout their life, it is likely to be useful to focus limited health care resources particularly to those who are the most vulnerable. Catching these individuals and preventing their next potential event will be key to reduce individual harm and societal expenses.

We underscore the fact that this program will not only validate new tools, but it will establish a new economically sustainable personalized treatment practice applicable throughout Europe particularly to those regions where CHD prevention needs upgrading.

A prospective well-designed randomized clinical trial (RCT) is the best strategy for directly measuring the impact (health, economic and social) of a novel treatment procedure. RCTs are expensive due to the large number of randomized patients needed for proving the significance of the chosen endpoints. Our cost-effective approach is to use an enrichment trial design guided by a validated ‘Biomarker Score’. This may be indeed the only way to conduct a cardiovascular prevention RCT within the constraints of a limited governmental budget. Enrichment improves the efficiency of our trial design by minimizing the required sample size and therefore allows us to perform a full clinical utility assessment of the personalized CHD prevention approach.

The proposed large scale prospective prevention trial will allow us to perform a careful assessment of the potential health economic benefits and social effects of the tested secondary prevention program. In addition, this design will produce appropriate and compelling evidence for regulators, policy makers and payers.

One of the core components of the trial intervention will be personalized coaching aiming at improving adherence to the guideline based optimized medical therapy and lifestyle changes including smoking cessation, increased physical activity and dietary changes. Key elements of coaching will be easy-to-use phone application and a web-based solution validated by our partners. Lifestyle programs are developed by the European Association of Preventive Cardiology (EAPC), a subsidiary society of the European Society of Cardiology, and this project will prospectively validate these existing programs to be adapted for modern platforms including easy to use mobile applications. Finally, after completing the prevention program all collected clinical, biomarker, lifestyle and hemodynamic data will be subjected to artificial intelligent (AI) analyses for further identification of crucial factors for success and failure in such personalized prevention program. This will allow us to design an effective tested prevention tool as the final outcome of this project. Our vison is that in future we can both amplify and personalize care at low cost with the help of mobile applications and software solutions allowing us to support growing numbers of CHD patients.

In addition to our prospective trial, we will analyze biobanked samples from existing large scale clinical trials to evaluate whether novel biomarkers can be used to better identify patients benefiting from the given drug treatments to improve the benefit to harm ratio. This work is motivated by our recent findings showing large response variability among statin users (unpublished) and results showing that the effect of ezetimibe depends on clinical risk This proposal version was submitted by Heli PEHRMAN on 02/10/2018 13:20:59 Brussels Local Time. Issued by the Participant Portal Submission Service. CoroPrevention 2018 2 stratification (Giugliano RP et al. Circulation. 2018 Apr 10;137(15):1571-1582). This would be particularly important for anti-thrombotic treatments saving lives, but also increasing the risk of major bleedings. Finally, recent developments in big data analyses allow us to efficiently screen databases for patient patterns including clinical characteristics, laboratory values or other biosignals that previously have remained undetected. We have access to a unique collection of digital electrocardiograms (ECG) linked to large health care registries and these data will also be included in the AI effort of this project. This will allow us to identify and validate additional automatically analyzable biosignals (ECG patterns) that can be used for patient stratification and treatment tailoring in addition to the laboratory measurements based clinical biomarkers.

The specific CoroPrevention objectives are:

1. Prospectively evaluate clinical utility of personalized prevention in CHD
2. Prospectively validate EAPC programs for prevention
3. Evaluate health economic and social benefits of the personalized prevention in CHD
4. Discover predictive markers of drug treatment response in CHD
5. Discover and validate ECG biosignals of high risk in CHD
6. Create a synthesis of the above findings constituting a novel prevention program to be applied across Europe
7. Bring the refined prevention program to the attention of practitioners, patients, health care payers and policy makers

Read more about the CoroPrevention Project here: https://coroprevention.eu

Summary of the CoroPrevention Project