Carotid artery disease, the primary trigger of ischaemic cerebrovascular events including stroke, causes major morbidity, mortality and healthcare costs worldwide. Still, treatment is based on criteria established in the 90s that do not take into account the molecular evolution we have witnessed since, nor the introduction of new medication, leading to remarkably high unnecessary surgical treatment while missing most patients at risk. TAXINOMISIS will provide novel disease mechanism-based stratification for carotid artery disease patients to address the needs for stratified and personalised therapeutic interventions in the current era. This will be achieved through (1) the dissection of mechanisms mediating carotid artery disease, and identification of susceptibility and protection factors of plaque erosion and/or rupture using longitudinal cohorts and multi-omics, (2) the definition of distinct disease phenotypes and endotypes, and generation of molecular fingerprints of high versus low-risk states through systems medicine, (3) the development of a multilevel risk prediction model of the symptomatic plaque incorporating new biomarkers and advanced imaging, implemented in a software, to assist patient stratification and clinical decision making, (4) the development of novel pharmacogenomics solutions based on lab-on-a-chip technology to support personalized treatment, (5) the evaluation of the new risk prediction model and lab-on-a-chip device in a prospective observational clinical study, and (6) the assessment of regulatory, cost-effectiveness and ethical issues towards the implementation and commercialization of the programme’s outcomes. TAXINOMISIS has therefore the potential to rationally change the current state-of-the-art in the stratification of patients with carotid artery disease by reducing unnecessary operations, refining medical treatment and opening up new avenues for therapeutic intervention, while strengthening the European biotechnology sector.

European Coronary Heart Disease (CHD) burden is 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 have planned to shape and implement a personalized secondary prevention program for patients with established CHD. This precision strategy will be tested in a prospective trial, the CoroPrevention Trial, a central element of our proposal. We aim to significantly reduce the numbers of coronary events by using outcome risk- and patient characteristics- guided prevention in CHD patients. 1. Prospectively evaluate clinical utility of personalized prevention in CHD 2. Evaluate health economic and social benefits of the personalized prevention in CHD 3. Discover predictive markers of drug treatment response in CHD 4. Improve current ESC guidelines based on RCT validated clinical data 5. Disseminate the refined prevention program to the attention of practitioners, patients, health care payers and policy makers This program will establish a new economically sustainable personalized treatment practice applicable throughout Europe particularly to those regions where CHD prevention needs upgrading. The used protocols and technologies will carefully assessed by NICE using their standard evaluation methods that will allow independent expert opinions for different European authorities and decision makers. These opinion statements will further be supported by full Health Economics analyses of CoroPrevention Trial.

Cardiovascular diseases (CVD) are the most common cause of death in Europe and world-wide. Optimizing CVD prevention is therefore of utmost importance, but personalized medicine has not yet reached clinical practice for CVD. Omega-3 polyunsaturated fatty acids (PUFA) are traditionally considered beneficial in CVD prevention. Clinical trials have however shown contradictory results for CVD outcomes. The aim of this project is to generate a personalized medicine CVD prevention decision tool to determine if omega-3 treatment is likely to be beneficial in individual patients, and what PUFA, dose, and formulation to use for an optimized response towards cardiovascular health. To this end, a multidisciplinary project is proposed integrating population-based genetic epidemiology, analyses of randomized clinical trials, nutrition, artificial intelligence (AI), lipidomics, and a clinical feasibility trial to identify the predictors of omega-3 PUFA responses. In five tightly connected work packages, the five partners of the consortium will explore well characterized cohorts and clinical trials for the interactions between genes, PUFA exposure, CVD risk and lipidomic markers towards beneficial CVD effects of omega-3 PUFA. Lipidomic methods, complementary between the partners, will be employed for mapping PUFA, PUFA sources, and PUFA-derived mediators as biomarkers. Data will be integrated using AI to develop the OmegaPerMed Prevention Tool for personalized medicine to optimize omega-3 PUFA treatment for CVD prevention, which will be continuously tested by a step-wise introduction of identified predictors in a pilot feasibility clinical trial. Ethical, legal, and social issues will be addressed throughout the project.The anticipated OmegaPerMed Prevention Tool for optimizing omega-3 treatment in CVD can hence be the first personalized medicine to be widely implemented in international CVD treatment guidelines to the benefit of large patient population in Europe and world-wide.