University of Pittsburgh

Novel Ticagrelor Coated Coronary Stent Using a Self-Assembled Monolayer Linker System

University of Pittsburgh researchers have developed a novel vascular stent with antiplatelet capabilities. The stent uses a self-assembled monolayer of 12-aminododecylphosphonic acid (ADPA) to attach the antiplatelet agent, ticagrelor, to its luminal surface. By providing focal anti-platelet therapy, this ticagrelor-coated stent (TCS) could revolutionize post percutaneous coronary intervention (PCI) therapy by eliminating the need for systemic anti-platelet therapy to prevent stent thrombosis, a serious post-PCI complication.  

A stent coated with a potent antiplatelet agent has been developed to deliver targeted therapy to prevent clot formation following coronary stent placement, removing the need for systemic antiplatelet therapy, and reducing bleeding risk.

Description

Around one million PCI procedures are performed each year in the United States as the first line of treatment for acute myocardial infraction. Stent thrombosis, where the stent becomes blocked by thrombotic occlusion (clots), is a catastrophic complication of PCI and is prevented by using prolonged systemic antiplatelet medication for up to one year post stent implantation. However, systemic antiplatelet therapy creates a high bleeding risk in certain patients. This novel stent can deliver targeted antiplatelet therapy reducing the risk of stent thrombosis while removing the need for systemic treatment and the associated side effects.

Applications

- Coronary stent thrombosis
- Acute myocardial infarction
- Atherosclerotic disease

Advantages

Current strategies to reduce stent thrombosis include systemic antiplatelet therapy. Additionally, many patients with stents have preexisting health conditions requiring anticoagulant therapy for stroke prevention. In these patients the use of multiple oral anticoagulation therapy increases the risk of post-PCI bleeding by up to 12%, which increases the risk of death.
This novel approach removes the bleeding risk associated with systemic anticoagulant use by directly delivering antiplatelet therapy within the stent. A known anticoagulant therapy, ticagrelor can be tethered to the surface of the stent using a chemical linkage with self-assembled monolayers. There are three key benefits – targeted delivery of antiplatelet therapy to stent site, reduction of blood-metal contact (known to increase clot formation), and the stability of the chemical linkage with ticagrelor prevents disaggregation, reducing the risk of systemic effects.

Invention Readiness

A prototype stent has been built. Diffuse Reflection Infrared Fourier Transform (DRIFT) spectroscopy demonstrated the linkage of ticagrelor to the self-assembled monolayer. In vitro experiments found a reduction in platelet attachment to the TCS compared with a bare metal stent. In vivo studies in two different animal models found stent retained patency up to 35 days after implantation without the use of systemic antiplatelet therapy.

IP Status

https://patents.google.com/patent/WO2020219894A1