Late Loss and Clinical Events

“The clinical impact of this phenomenon does not affect the long-term efficacy and longevity of the intracoronary radiation therapy when compared with conventional therapeutic approach.”¹ The delayed in-stent lumen loss may also be related to the significant aggressive pattern of in-stent restenosis (ISR) (diffuse-proliferative or total occlusion) in 80% of these patients. Nevertheless these elegant quantitative methods (QCA and IVUS) give us an understanding of the process involved, which may affect the long-term clinical result. In the Mehran paper, the target lesion revascularization (TLR) rate at one year after conventional treatment for these patterns of ISR went from 34.5% to 83.4%, which was related to a much higher angiographic restenosis rate than was documented in this study.² Intracoronary brachytherapy is still the only nonsurgical treatment of in-stent restenosis proven to be superior to conventional treatment. In numerous randomized, placebo-controlled trials involving in-stent restenoses, intracoronary brachytherapy showed significant improvement in angiographic and clinical outcomes. Intracoronary brachytherapy has been shown to be effective for the treatment of in-stent restenosis with gamma and beta radiation. START (beta radiation, similar to the one used in this study, but of 30 mm length only) was the first randomized, controlled trial with beta radiation showing a significant reduction of clinically-driven target vessel revascularization (TVR) rates after eight months, from 26.8% to 17.0%.³ These results reflected the “real world” situation as confirmed by the European RENO registry involving 1,098 consecutive patients, with a clinically-driven TVR rate of 15.6%.⁴ It has been recently reported that the initially beneficial outcome effects of intracoronary brachytherapy with beta-radiation using 90 Sr/90Y for in-stent restenosis are maintained during a two-year follow-up period.⁵ The follow-up rate at two years (± one month) of approximately 80% in both the treatment and placebo arms is comparable to other radiation studies. At two-year follow-up after brachytherapy, the clinical outcome remains significantly improved, with a freedom from TVR rate of 72.5%, and a freedom from MACE rate of 68–69%. The improvement of clinical outcomes begins at about 90 days after radiation. This is comparable to other beta-emitters and to gamma radiation.⁶ Previously, many concerns have been raised regarding the possibility of late radiation-associated adverse events: the risk of delayed and accelerated vascular disease, aneurysm formation, late thrombosis and late lumen loss. The follow-up period of two years has shown that these adverse events did not occur clinically. Only one radiated patient developed a stent thrombosis between one month and two years. This rate of late stent thrombosis of 0.4% is well within the range of late stent thromboses of 0.7% in patients who did not receive brachytherapy.⁷ The relationship between late luminal loss and angiographic restenosis seems to be consistent; the relationship between late luminal loss and clinical outcome follows a threshold pattern as has been demonstrated even in the drug-eluting stent (DES) studies.⁸ This phenomenon may explain the result of this study: preservation of the clinical effect despite the increase in late luminal loss at one year.¹ Intracoronary radiation has lost its usefulness for the treatment of in-stent restenosis with the availability of DES, even if we do not disregard the results of randomized studies comparing DES and radiation.

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