Endovascular manipulation to restrict restenosis

The processes that take place following damage to the vessel wall are well understood. Endovascular manipulation by its very nature induces such damage and the repair process can lead to a recurrence of symptoms. There have been many clinical trials of drugs chosen for their known impact on preventing excess vessel wall response. With one or two exceptions none of these trials has shown any benefit, partly because only low doses could be given systemically to avoid side effects. Local drug delivery allows high doses to be given where needed, at the site of the process, without inducing systemic complications. There are various drugs and agents that have been shown to be effective in models of vessel wall damage, including heparin, nitric oxide, inhibitors of platelet function and the antisense oligonucleotides. Some of these agents are now being tested in clinical trials. Methods of delivering the agent include devices that bathe the luminal layer, deliver the agent to the media or inject it into the adventitia where a reservoir can form. Stents improve the outcome after angioplasty, but can also induce a proliferative vessel wall response. To overcome this, stents have recently been considered as local delivery devices with radiation being delivered and polymer coated stents, loaded with agents, being developed. While local drug delivery provides great promise as a way of reducing the adverse effect of response of the vessel wall to damage, the results of clinical trials in humans are awaited.