The influence of statins on the role of blood coagulation in the maintenance of a healthy macro- and microvasculature and in the prevention of recurrent thrombosis.

1. The influence of statins on the role of blood coagulation in the maintenance of a healthy macro- and microvasculature and in the prevention of recurrent thrombosis. Harry R. Büller, MD, PhD (AMC) and Pieter H. Reitsma, PhD (LUMC)

2. S. Middeldorp MD, PhD/J.C. Meijers PhD, AMC H. ten Cate MD, PhD/T. Hackeng PhD, MUMC F.R. Rosendaal MD, PhD/H.H. Versteeg PhD, LUMC K. Meijer MD, PhD/T. Lisman PhD, UMCG F. Leebeek MD, PhD/M. de Maat PhD, ErasmusMC Consortium The PIs and their collaborators represent all key researchers in the Netherlands in the field of hemostasis and thrombosis. Basic scientists in hemostasis/ thrombosis (Hackeng, Heemskerk, Spek, Van ‘ t Veer, Versteeg, De Groot, Meijers, Lisman, de Maat, van Heerde etc.), excellent epidemiologists (Rosendaal, Prins, Lijfering, and Cannegieter etc.) and seasoned clinical investigators (Ten Cate, Middeldorp, Leebeek, Huisman, Meijer etc) are brought together. The two research leaders are in their respective fields established opinion leaders and share relevant overlap. UUMC UMC St Radboud

5. Research plan WP-1 Digging deeper: Investigating in-vivo/in-vitro the role of blood coagulation components and anti-thrombotic drugs in endothelial barrier function and atherosclerosis WP-2 Exploring new frontiers: Investigating in-vivo/in-vitro the effects of statins on blood platelets, blood coagulation/fibrinolysis and the thrombotic phenotype of the vascular wall WP-3 Probing the link: validating uncovered critical mechanisms in a clinical trial using statin treatment for prevention of recurrent venous thrombosis WP-4 Shaping the future: Development of predictive models of recurrent venous thrombosis and arterial thrombosis and analysis of its cost- effectiveness

6. Translation The research plan is divided in four workpackages, of which two (WP1-2) focus on fundamental aspects of the research questions, a third is devoted to the DuLac clinical trial (WP-3) and the last deals with translation of the findings to models of clinical decision making (WP-4). Discoveries in WP1 and -2 will be tested, validated, and subsequently further investigated with the help of WP-3 and -4 (bench-bedside-bench).