Restenosis postangioplasty: Role of local drug delivery on its prevention

Restenosis is a complex reparative process that involves several redundant and overlapping mechanisms. The sequence of events leading to restenosis after balloon angioplasty can be divided into three distinct phases: a) recoil, both acute and chronic as in vessel remodeling, b) thrombosis, and c) smooth muscle cell activation with synthesis of extracellular matrix. Attempts at preventing restenosis in humans have been frustrating and disappointing. One of the reasons for this lack of success has been the difficulty of achieving high local, levels of a pharmacological agent following its systemic administration. With the advent of endovascular stenting, the local targeting of pharmacological agents has become an important therapeutic consideration for treating restenosis. Current local delivery approaches can be classified as balloon-based devices, coated stents and endovascular polymers, and those involving molecular biology and gene therapy.