Increasing the dose of gamma radiation by 21.4% as an adjunct of percutaneous coronary intervention in patients with in-stent restenosis can improve outcomes, according to results of the SCRIPPS-IV trail.

Although only modest improvements were seen in angiographic indices and restenosis, increasing the dose from 14 Gy to 17 Gy resulted in substantial improvements in total lesion revascularization (TLR) total vessel revascularization (TVR) and major adverse cardiac events (MACE), said paul S. Teirstein, MD, who presented the results at yesterday¡¯s late-breaking clinical trials session. ¡°A dose-response relationship has been demonstrated for vascular gamma radiation therapy¡±, Dr. Teirstein said. ¡°Increasing the currently recommended dose prescription from 14 Gy to 17 Gy should be strongly considered, particularly in high restenosis-risk subgroups, such as patients with diabetes¡±.

Early gamma radiation trials used low radiation doses. More recent trials began to use higher doses and the Scripps researchers wondered if the current recommendation of 14 Gy was just on the borderline of efficacy for gamma radiation, Dr. Teirstein said. The purpose of the SCRIPPS-IV trial was to compare the safety and efficacy of a 21.4% increase from 14 Gy to 17 Gy for patients with in-stent restenosis. For the double-blind, randomized trial, researchers enrolled 358 patients at two sites: the Scripps Clinic and Lenox Hill Hospital. Patients had in-stnet restenosis of native or vein grafts, with lesions up to 76 mm in length. Patients also received clopidogrel (Plavix, Sanofi Synthelabo) and aspirin for six months if they did not receive a new stent, and for a minimum of 12 months if they did receive a new stent. About 10% of patients in each group received new stents. Dr. Teirstein explained that most of the patients had already received what he called a great number of procedures. ¡°These were the frequent-flyers to the cath lab¡±, he explained. Researchers performed an angiogram follow-up at eight months. Baseline characteristics were similar between treatment groups, although the proportion of men and patients with diabetics was slightly higher in the 17-Gy dose.

¡°The angiographic results were interesting¡±, he said. There was a modest but significant reduction in the incidence of late loss associated with the use of 17 Gy. There were more modest result with restenosis: a 36% reduction in in-stent restenosis and an 18% reduction in in-lesion restenosis with the higher radiation dose. ¡°These modest reductions translated into much more dramatic reductions in clinical endpoints¡±, Dr. Teirstein said. Patients in the 17-Gy arm experienced a 44% reduction in TLR and a 36% reduction in TVR. Mortality was low in both groups, but patients in the higher radiation dose had a dramatic reduction of 41%, Teirstein said. There was not an increase in adverse events, according to the study. The rates of thrombosis were identical and low in both groups at 1.2%. ¡°What was most surprising was the reduction in total occlusions¡±, Dr. Teirstein said. As the radiation dose increased from 14 Gy to 17 Gy, the rate of total occlusions decreased from 9.7% to 2.4%. ¡°Using the higher dose seemed to abolish the problem of late total occlusion at follow-up and seemed to bring the numbers down to low rates, he said.