Triggers of atherothrombosis in peripheral artery disease (PAD)
In this partnership between Bayer and CARIM the contribution of “contact” activation is studied, in particular of kallikrein, in patients with peripheral artery disease (PAD) at risk of thrombosis using state of the art laboratory techniques.
Over 200 million patients worldwide suffer from peripheral artery disease (PAD), characterised by systemic atherosclerosis, and are at very high risk of death from myocardial infarction or ischemic stroke (combined 15% annually). Prevention of these complications is done with antiplatelet agents; the addition of an anticoagulant like rivaroxaban can further reduce the burden of disease, however the risk of major bleeding is still substantial. This project hopes to find reasons for further developing drugs against “contact factors” like kallikrein, that could provide an effective but safer (less bleeding) type of anticoagulant. This may have substantial consequences for safety and costs related to antithrombotic management of PAD patients.
The contact and intrinsic pathway biomarkers in blood from 287 (article is under submission to a scientific journal) were measured. Unfortunately, none of the contact system biomarkers predicted the primary clinical outcome (combined endpoint of MI, stroke, death, or elective vascular intervention). Only thrombin-antithrombin complex levels that reflect ongoing clotting activation more centrally located in the coagulation system, were significantly higher in patients with an event within one year follow up (in total ± 10 % of patients), as compared to those without event. After adjustment of sex and age, this difference was no longer significant. This means that from the circulating blood of patients with PAD, no clear link between contact activation and clinical outcome is derived. Hence, the development of medication particularly for this purpose, is not supported by current data. They are still exploring whether in the vessel wall of PAD patients that underwent surgery, a more localised contribution of contact factors may be detected; due to Covid-19, these studies were delayed and analyses are still ongoing in collaboration with Bayer, also exploring novel inflammation markers linked to coagulation.
