The restenosis story: is intracoronary radiation therapy the solution?

Restenosis remains a major limitation of percutaneous transluminal coronary intervention. Stenting made an important contribution in restenosis reduction, but in-stent restenosis is becoming a growing problem. Although radiation therapy was traditionally used to kill relatively fast-growing tumor cells, it has also been used to clinically treat benign but problematic hyperplastic conditions. In addition, in vitro studies have shown that radiation inhibits serum-stimulated growth of arterial smooth muscle cells and fibroblasts, and decreases collagen synthesis by fibroblasts. The effects of radiation on neointimal inhibition after vascular injury were investigated in animal models using various catheter- and stent-based endovascular approaches (brachytherapy) as well as externally delivered x-irradiation. These studies have consistently shown that ionizing radiation delivered by the endoluminal approach results in remarkable suppression of neointima formation. However, animal studies also demonstrate altered vessel wall healing with increased thrombogenicity. The catheter-based approach with gamma- or beta-emitters showed feasibility and appears promising in early human clinical trials, whereas the strategy of using radiation stents is more problematic in the clinical arena. A number of randomized multicenter trials have been initiated and the results are eagerly awaited. More work needs to be done to define the optimal dosage, and to study the short- and long-term vascular biologic effects of brachytherapy. Additionally, if this form of therapy proves efficacious in the large, randomized, clinical trials, its cost-effectiveness will then need to be established. This review touches on some of the basic concepts involved in using the strategy of endovascular irradiation therapy for restenosis prevention after percutaneous coronary intervention and reviews the evidence of clinical efficacy and safety.