Editorial Commentary: <br />
In-stent Restenosis and Cutting Balloon

In-stent restenosis (ISR) is the most important limitation to current percutaneous coronary intervention (PCI) practice. Intimal hyperplasia has been well defined as the principal mechanism involved in recurrence after stent implantation. Although several different strategies (devices and drugs) had been tested in past years aiming to decrease the intimal hyperplasic response, the definite therapy for ISR has not yet been established. Mehran et al.1 indicated that the angiographic ISR pattern is an independent predictor of recurrence after ISR treatment. Increasingly worse prognosis correlated with diffuse intrastent, proliferative and totally occlusive ISR lesions. In this issue of the Journal, Braun et al. showed cutting balloon (CB) to be superior to rotational atherectomy (RA) for the treatment of long ISR lesions. The CB group had significantly lower clinical (18.7% vs. 43.2%; p See Braun et al. on pages 291–296 between-group differences in baseline characteristics were not statistically significant, it is probably important to point out that the RA group had marginally smaller reference diameters, longer lesion lengths, and more LAD lesions than the CB group. Although CB and RA have not been compared before, each one has been compared to other techniques of ISR treatment. RA has been found to be similarly effective to excimer laser angioplasty for ISR, despite its higher ablation efficiency; this study indicated the rather small contribution of ablative techniques for ISR.2 In the randomized ARTIST trial,3 RA showed to be inferior to conventional balloon PTCA in the treatment of ISR. Although the restenosis rate in the ARTIST RA group (65%) was similar to the one reported by Braun et al., the restenosis rate for the conventional balloon arm (51%) was much higher than the CB group in the current analysis showing a probable superiority of CB over conventional balloon PTCA as well. This is similar to the findings of Adamian et al.,4 who reported the CB technique to be an independent protective predictor of event-free survival when compared to conventional balloon, stent or RA for the treatment of ISR. Diffuse ISR pattern was predictive of recurrence in the same analysis. However, this interventional landscape has been changed after the emergence of intravascular brachytherapy (IVBT), which was shown to be very effective in reducing recurrence after ISR treatment in prospective randomized trials.5,6 The efficacy of IVBT for long ISR lesions was showed in two different randomized trials.6,7 Currently, IVBT should be considered the standard therapy for ISR treatment. Therefore, the question remains: which is the preferred interventional technique for ISR treatment in conjunction with IVBT? Initial results suggest that a “synergy” between IVBT and CB for ISR therapy may indeed be present.7 The foundation for CB superiority over conventional balloon pre-IVBT seems to be the absence of slippage and the more effective (“powerful”) tissue extrusion. Avoidance of unwanted expansion of the injury zone due to balloon slippage may be very important in limiting “geographical miss” and edge dissections. Nonetheless, the most effective therapy of ISR is to prevent its occurrence in the first place. Drug-eluting stents (DES) are demonstrating very impressive results for treatment of de novo coronary lesions. However, results may not be as perfect when ISR lesions are targeted,8 for reasons that are not so well understood yet. This important question will likely be addressed in future DES trials, specifically designed for ISR.

1. 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. 2. Mehran R, Dangas G, Mintz GS, et al. Treatment of in-stent restenosis with excimer laser coronary angioplasty versus rotational atherectomy: Comparative mechanisms and results. Circulation 2000;101:2484–2489. 3. vom Dahl J, Dietz U, Haager PK, et al. Rotational atherectomy does not reduce recurrent in-stent restenosis. Results of the Angioplasty versus Rotational Atherectomy for Treament of diffuse In-Stent restenosis Trial (ARTIST). Circulation 2002;105:583–588. 4. Adamian M, Colombo A, Briguori C, et al. Cutting balloon angioplasy for the treatment of in-stent restenosis: A matched comparison with rotational atherctomy, additional stent implantation and balloon angioplasty. J Am Coll Cardiol 2001;38:672–679. 5. Leon MB, Teirstein PS, Moses JW, et al. Localized intracoronary gamma-radiation therapy to inhibit the recurrence of restenosis after stenting. N Engl J Med 2001;344:250–256. 6. Waksman R, Raizner AE, Yeung AC, et al. Use of localised intracoronary beta radiation in treatment of in-stent restenosis: The INHIBIT randomised controlled trial. Lancet 2002;359:551–557. 7. Waksman R, White RL, Chan RC, et al. Intracoronary-radiation therapy after angioplasty inhibits recurrence in patients with in-stent restenosis. Circulation 2000;101:2165–2171. 8. Kobayshi Y, Balan O, Arif F, et al. Cutting balloon angioplasty followed by gamma radiation for in-stent restenosis (Abstr). Circulation 2001;104:II-416. 9. Serruys PW, Abizaid A, Foley D. Sirolimus-eluting stents abolish neointimal hyperplasia in patients with in-stent restenosis: Late angiographic and intravascular ultrasound results (Abstr). J Am Coll Cardiol 2002;39(Suppl A):823–831.