Despite remarkable progress in the management of cardiovascular disease (CVD), major unmet needs remain with regard to mortality, hospitalisations, quality of life (QoL), healthcare expenditures and productivity. Acute coronary syndrome (ACS), atrial fibrillation (AF) and heart failure (HF) are major and growing components of the global CVD burden. Optimal management of these conditions is complicated by their complex aetiology and heterogeneous prognoses. Poor definition at the molecular level and co/multi-morbidities form major challenges for the development and delivery of targeted treatments. This renders response to therapy unpredictable, with large inter-individual variation and, importantly, small or undetectable treatment effects in large trials of unselected patients. Today’s treatment guidelines still reflect the scientific constraints of an earlier era where clinical markers to guide therapy are limited to conventional risk factors and end-organ damage, and where the main endpoint in clinical trials is patient death. Hence, drug development pipelines from early target validation through to late post-marketing work have proven to be slow, expensive and high-risk: the chance of eventual approval for a CVD drug candidate in Phase I trials is 7%, the lowest of any disease category (shared with oncology) 2. Moreover, tolerability of medication and adherence to treatment show wide variations. There is thus a need for better definition of these diseases, their markers and endpoints (including better segmentation of current heterogeneous patient groups acknowledging underlying mechanisms and comorbidities) and of their outcomes/prognoses (including functional capacity and quality of life [QoL]). BigData@Heart’s ultimate goal is to develop a Big Data--driven translational research platform of unparalleled scale and phenotypic resolution in order to deliver clinically relevant disease phenotypes, scalable insights from real-world evidence and insights driving

Patients with acute ischemic stroke and atrial fibrillation are at high risk for recurrent stroke and other adverse cardiovascular complications. Usual care comprises oral anticoagulation and rate control. However, it is unclear, whether existing interventions for early rhythm control reduce the risk of adverse cardiovascular outcomes in these vulnerable patients. EAST-STROKE (Early treatment of Atrial fibrillation for Stroke prevention Trial in acute STROKE) is set out to tackle and reduce the individual and societal burden of death and disability by providing evidence for effective secondary prevention using readily available interventions in these patients. To this end, EAST-STROKE is an investigator-initiated, prospective, randomized, open, blinded endpoint assessment (PROBE) multi- trial to test whether early rhythm control therapy prevents adverse cardiovascular outcome in patients with acute ischemic stroke and atrial fibrillation compared to usual care. Up to 1,746 patients will be enrolled. Trial organisation relies on a network of experienced clinical researchers, patient representatives and Health Economics experts. Outcome evaluation will involve a comprehensive array of clinical and safety parameters, health and socio-economic outcomes including patient reported outcome measures. We will also perform cost-effectiveness analyses to address the needs of payers and ease implementation into reimbursement schemes. The project addresses a major health burden and will provide evidence for more effective prevention of adverse outcomes in an area of high public health need. We expect that the results of EAST-STROKE will be implemented rapidly throughout Europe, will support health equity, and will prevent more than 150 thousand recurrent strokes or adverse cardiovascular outcomes over a period of five years. By this, EAST-STROKE will lead to significant cost-savings to European health systems and societies.

TENSION (efficacy and safety of ThrombEctomy iN Stroke with extended leSION and extended time window: a randomized, controlled trial) strives at providing innovative treatment to patients with severe stroke to reduce the individual and societal burden of death and dependency from stroke. To this end, TENSION is a randomized, controlled, prospective, open label, blinded endpoint (PROBE) trial of thrombectomy in stroke patients with extended ischemic stroke lesions and patients presenting in a late time window, who are currently excluded from available effective treatment approaches. The trial will enroll up to 714 subjects in eight European countries. The primary endpoint is functional outcome at 90 days post-stroke measured by the Modified Rankin Scale. The primary effectiveness endpoint analysis is a chi-square test of the difference in linear trends in ordinal mRS outcomes between treatment groups (“mRS shift analysis”). Outcome evaluation will involve a comprehensive array of clinical and safety parameters, health and socio-economic outcomes including patient reported outcome measures (PROM) for evaluation according to the principles of value-based healthcare. Health economic evaluation with cost-effectiveness analysis will be performed and gender-effects on treatment and outcome will be studied. Trial organization will rely on a network of experienced partners with successful cooperation in previous EU-funded stroke trials. An image core lab will provide central judgement of all images acquired within the trial. Standards of image judgement and intervention will be defined and trial specific training will be provided to all investigators. TENSION addresses a major health problem and will provide evidence for more effective and safer therapeutic intervention for patients with severe stroke resulting in improved guideline development, better individual patient outcomes and beneficial effects for the society at large by reduction of stroke-related costs.