Beta-radiation to reduce restenosis. Too little, too soon?

With almost 1 million procedures undertaken worldwide each year, coronary angioplasty is flourishing. This elegant technique, however, continues to be plagued by a restenosis rate of 30% to 60%.1 Efforts to reduce restenosis have been herculean. Literally, scores of pharmaceutical agents have been tested in clinical trials.2 3 4 Despite initial promising results in experiments with animals, each clinical trial has been a disappointment. Coronary stents stand alone as the only intervention that has been proved to decrease restenosis. In the STRESS and BENESTENT trials, the implantation of a single Palmaz-Schatz coronary stent was associated with a 30% reduction in restenosis rates.5 6 The impact of stents on restenosis, however, is purely mechanical.7 8 Stent implantation expands the vessel lumen further than the use of balloon angioplasty alone. This larger lumen creates more space for the still ubiquitous intimal proliferation. Stents do not diminish the cellular response to injury. In fact, the proliferative response, as measured on the basis of late loss after the procedure, is actually increased by the use of stents. Stents decrease restenosis by simply increasing the capacity of the artery to tolerate intimal proliferation. Despite extensive clinical testing, no agent has been shown to inhibit the proliferative component of restenosis. Radiotherapy is the latest in a long line of potential antiproliferative agents to be enthusiastically tested as an adjunct to angioplasty. There is much to recommend the use of radiotherapy in the fight against restenosis. In more than 100 years of clinical experience, radiotherapy has proved to be highly effective in inhibiting cellular proliferation, in both malignant and benign disease. Examples of benign hyperplastic entities that have been effectively treated with radiotherapy include the exuberant fibroblastic activity of keloid scar formation, heterotopic ossification, desmoid/aggressive fibromatosis, Peyronie's disease, and pterygium.9 10 11 …