Late Loss and Clinical Events

Raoul Bonan, MD
Raoul Bonan, MD
“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.
1. Feres F, Munoz J, Abizaid A, et al. Angiographic and intravascular ultrasound findings of the late catch-up phenomenon after intracoronary beta-radiation for the treatment of in-stent restenosis. J Invasive Cardiol 2005;17:473–477. 2. Mehran R, Dangas G, Abizaid AS, et al. Angiographic patterns of in-stent restenosis: Classification and implications for long term outcome. Circulation 1999;100:1872–1878. 3. Popma JJ, Suntharalingam M, Lansky AJ, et al. Randomized trial of 90Sr/90Y beta-radiation versus placebo control for treatment of in-stent restenosis. Circulation 2002;106:1090–1096. 4. Urban P, Serruys P, Baumgart D, et al. A multicentre European registry of intraluminal coronary beta brachytherapy. Eur Heart J 2003;24:604–612. 5. Silber S, Popma JJ, Suntharalingam M, et al. Two-year clinical follow-up of 90Sr/90Y ß-radiation versus placebo-control for the treatment of in-stent restenosis. Am Heart J 2005;149:689–694. 6. Waksman R, Ajani AE, White RL, et al. Two-year follow-up after beta and gamma intracoronary radiation therapy for patients with diffuse in-stent restenosis. Am J Cardiol 2001;88:425–428. 7. Kalaria VG, Ling FS. Late stent thrombosis without antecedent brachytherapy: confirmation and treatment with rheolytic thrombectomy. Catheter Cardiovasc Interv 2001;53:243–247. 8. Mauri L, Orav EJ, Kuntz RE. Late loss in lumen diameter and binary restenosis for drug-eluting stent comparison. Circulation 2005;111:3435–3442.