Surgery to restore blood flow in arteries blocked by atherosclerotic plaque is a common treatment in cardiovascular disease. Long-term complications of surgical treatment are vein graft disease and restenosis, a renarrowing of the blood vessel after bypass or removal of the culprit atherosclerotic plaque. Attempts to prevent or treat these complications by systemic pharmacological approaches have been largely unsuccessful in the clinic. This has led to an interest in developing targeted or

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... ly delivered strategies. This paper discusses many of the various site-delivered therapies that are under examination as potential antirestenotic and antivein graft disease agents (including antithrombotic, antiproliferative, and anti-inflammatory agents) and why many therapies developed in animal models fail in clinical trials. Techniques of targeted delivery (including stents, "magic bullets," and adventitial delivery) and delivery systems (including nanoparticles and the use of gene therapy) are also discussed.