START

Statins Reduce Thrombophilia Study

Project managers

Dr W.M. Lijfering
Dr S.C. Cannegieter
Dr F.J.M. van der Meer
Prof. dr F.R. Rosendaal

CooperationLeiden Anticoagulation Clinic and Bioinformatics, and
Department of Clinical Medicine, University of Tromsø, Norway
InformationW.M.Lijfering@lumc.nl

Venous and arterial thrombosis are traditionally regarded as two different diseases with respect to pathophysiology, epidemiology and treatment strategies. Research findings of the past few years suggest that this categorical distinction may be too strict. However, whether the described relationship between venous and arterial thrombosis is real or a result of other factors such as confounding, chance or bias is still unclear. The overall objective of the START project is to understand the etiology behind the supposed relationship between venous and arterial thrombosis and to study whether and how statin use can decrease (recurrent) venous thrombosis risk. Several complementary studies are carried out simultaneously, each targeting different aspects of this association. 

  1. A cohort study amongst inhabitants of the city of Tromsø, Norway, will yield 1) whether the presence of atherosclerosis, based on time dependent measurements, increases the risk of venous thrombosis, while taking confounding or modifying factors such as statins into close account, and 2) whether venous thrombosis increases the risk of atherosclerosis either directly or through confounding or modifying factors. This study is performed within the Tromsø Study, a large prospective cohort study that was initiated in an attempt to help combat the high mortality of cardiovascular diseases in Norway.
  2. A cohort study amongst 5000 patients who had previously participated in a large population-based case-control study (MEGA-Study) to determine the effect of statin use on the risk of a recurrent venous thrombosis.  
  3. A randomized study, in collaboration with the Leiden Anticoagulation Clinic, to determine whether patients with a first venous thrombosis are less hypercoagulable when put on rosuvastatin.

When the results of the 3 key aims proposed here turn out negative, we can conclude that the existence of a direct causal effect of statins on prevention of venous thrombosis is unlikely. Thus, unfounded enthusiasm for this therapy will be avoided, as well as all efforts and expenses of a large randomized clinical trial. In contrast, if the results of these studies turn out positive, this will indicate that a causal effect of statins on venous thrombosis is probable. This will form a solid basis for the final step, i.e. a randomized clinical trial into the effect of statins on prevention of venous thrombosis. Such a study will change clinical decision making, that is: whether patients at high a-priori venous thrombosis risk should or should not be treated with statins.

This so-called START-project was funded by the Netherlands Heart Foundation (www.hartstichting.nl/).