European heart specialists develop new concepts to prevent stent thrombosis Millions of cardiac patients worldwide depend on stents for the treatment of blocked blood vessels. In 2010 more than 1.2 million stent implantation procedures were conducted in Europe. However, a small but important minority of successfully-treated patients may subsequently develop abrupt stent failure – a life-threatening complication known as stent thrombosis. This occurs when the stented vessel fills suddenly with blood clot. The abrupt disruption in blood supply is life-threatening for the patient and fatal in up to 50% of all cases. Indeed it is estimated that every year around 25,000 patients die of stent thrombosis. The exact underlying mechanisms and risk factors leading to stent thrombosis remain unclear and more research in this area is urgently needed. Since 2010 a consortium consisting of 14 European institutions have come together to address this critically important issue. The project they are working on is known as PRESTIGE – which stands for “PREvention of late Stent Thrombosis by an Interdisciplinary Global European effort” – and is coordinated by the German Heart Centre in Munich. It is planned to run for four years from 2010 to 2014. The investigators fought off stiff competition to secure funding from the European Commission to the tune of 6 million Euros. Within the project the scientists want to develop new concepts to identify and prevent stent thrombosis. The strategy includes a basic-scientific approach to decrypt the molecular and cellular mechanisms underlying stent thrombosis as well as a bioengineering approach focused on the development and testing of new stent materials to prevent this serious complication. New materials for stents to prevent stent thrombosis A stent is an open metallic tube which is used by interventional cardiologists to open-up blocked arteries. It is coated with a mixture of medications and polymer, which prevent potentially damaging scar tissue formation that can otherwise form on the stent in the initial months after implantation. One downside of these highly effective “drug-coated stents” is that in a small minority of cases the stent coating itself might cause an inflammatory reaction. Inflamed vessels attract platelets – the tiny cells that set off blood clot formation – and this could be an important trigger for stent thrombosis. The development of new stent material and coatings – targeted at reducing the risk of stent thrombosis – is a key focus of the project. In order to do this scientists must first better understand how stent surfaces interact with blood platelets, and this is the focus of the basic science work package in PRESTIGE. The next step is to translate the lessons learned into the development of new devices that will benefit patients. One approach is to focus on developing alterative medication and polymer coatings with a lower risk for inflammation after implantation. Initial results with modified polymer-coated stents look promising. Testing of these stents in patients is already at an advanced stage and the results from this part of the PRESTIGE project have so far been very encouraging. In a second approach the scientists are investigating a completely different strategy. In order to minimize the risk of blood platelets sticking to the stent, the researchers are working on methods to encourage the body to cover the stent surface with a healthy layer of normal cells. To do this they lined stents with thin layers of protein antibodies that work by attracting healthy cells and anchoring them to the surface of the stent. Once the stent is covered by a layer of the body’s own healthy cells, the chance of platelets sticking to the stent is very low and accordingly the risk of stent thrombosis is significantly reduced. Initial results with these antibody-modified stents in the laboratory were very encouraging and in the next step the investigators will trial these stents in patients.
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