Prevention of coronary restenosis with radiation therapy: a review

The problem of restenosis after percutaneous transluminal coronary angioplasty remains the major limiting factor of the procedure. Over the last 10 years, investigators have been studying the use of radiation therapy for preventing restenosis after angioplasty or stent placement. Since radiotherapy has been proven in other cases to be effective in disrupting the cell cycle regulatory proteins and thereby slowing or stopping growth, it was decided to apply the same principle to neointimal hyperplasia. To review the data that have emerged regarding vascular radiation with an emphasis on irradiated stents, 65 articles were reviewed and both preclinical and clinical experiments were included. Overall, studies with gamma and beta radiation show promising results. Endovascular gamma radiation has been shown effective in randomized trials, even at 3-year follow-up. Beta radiation is preferred because of greater safety and localization, and because it has also shown encouraging results in initial clinical trials, as well as in larger randomized studies. Consequently, the Federal Drug Administration has approved the use of both. In both types of endovascular brachytherapy, it seems the greater the dose, the better the initial response. Safety concerns include an increased incidence of late thrombosis and greater restenosis at margins. With irradiated stents, however, the situation is not as clear. At times, animal models have presented confusing results. These have ranged from significant suppression of hyperplasia to outright adverse effects of radiation on the vessel wall. While some clinical trials have been encouraging, others have not. Follow-up of up to 1 year has been disappointing so far. Many issues, such as the "candy wrapper" effect and rebound hyperplasia, must be dealt with before this becomes a viable form of therapy. It has become clear that radiation therapy in this setting, while having potentially great benefits, can cause deleterious effects as well. However, the mixed bag of positive and negative results seen so far, and the attractiveness of stents or percutaneous transluminal coronary angioplasty being "restenosis-proofed," eventually is cause for cautious optimism.