Response to Letter Regarding Article, “Paclitaxel-Coated Balloon Catheter Versus Paclitaxel-Coated Stent for the Treatment of Coronary In-Stent Restenosis”
We appreciate the comments by Dr Alfonso and colleagues on the Paclitaxel-Eluting PTCA-Balloon Catheter in Coronary Artery Disease II (PEPCAD II) trial. Intracoronary radiation was the first successful treatment option for in-stent restenosis avoiding the stent-in-stent approach. However, implantation of a second (drug-eluting) stent has since become the first treatment option for in-stent restenosis. The implantation of a drug-eluting stent in a restenotic stent results in better acute lumen gain and lower restenosis rates compared with conventional balloon angioplasty or brachytherapy.1,2
The main determinant of restenosis after coronary stent implantation is neointimal hyperplasia. Other factors such as elastic vessel recoil and negative remodeling have no relevant impact on this scenario. Therefore, late lumen loss has been accepted as the most important measure for evaluating stent-based local drug delivery by angiography. For comparability, this measure has to be used to evaluate new antirestenotic treatments. Therefore, we decided to assess the efficacy of a drug-eluting stent or a drug-coated balloon in the treatment of coronary in-stent restenosis using the same angiographic measure.
We agree with Dr Alfonso et al that late lumen loss has obvious limitations in comparing stent implantation and balloon angioplasty. The advantage of stent implantation over angioplasty in short-term results is well known and was also seen in our trial. Despite the lower late lumen loss in the drug-coated balloon group, the difference between the 2 treatments in angiographic and clinical end points is not explained by the average minimal lumen diameter at follow-up. However, frequency distribution of the in-segment minimal lumen diameters shows a slight parallel shift at follow-up in the drug-coated balloon group versus a shoe-shaped configuration in the drug-eluting stent group. This means that almost all patients in the drug-coated balloon group benefited from non–stent-based local drug delivery to a similar extent. In the drug-eluting stent group, the majority of patients had a clear benefit from stent-based sustained drug release. However, a subgroup of patients did not respond to this therapy (Figure 1 in the article3). This difference between the 2 groups explains the results with regard to secondary angiographic parameters, such as binary restenosis rate and clinical outcome.
First-in-human data on the treatment of coronary in-stent restenosis using the prototype “Paccocath” balloon are available from 2 randomized studies with identical designs. A total of 108 patients were enrolled: 52 patients in the Treatment of In-Stent Restenosis by Paclitaxel-Coated Balloon Catheters (Paccocath ISR I) trial4 and 56 patients in the Paccocath ISR II trial.5 Patients enrolled in the second trial were older, were more often female, had a higher incidence of diabetes mellitus, and had longer lesions than the patients included in the ISR I study. In-segment late lumen loss in the drug-coated balloon groups was 0.03±0.48 mm and 0.18±0.41 mm, respectively,4,5 which compares well with the late lumen loss seen in the present study using a newer-generation drug-coated balloon.
In conclusion, treatment of coronary in-stent restenosis with a drug-coated balloon avoids the stent-in-stent approach with the introduction of a second layer of metal in a native coronary artery. Furthermore, it reduces the need for antiplatelet therapy. Finally, the PEPCAD II trial showed favorable angiographic measures for the drug-coated balloon compared with a drug-eluting stent in this indication.
Prof Scheller and Prof Speck are coinventors of a patent application for various methods of restenosis inhibition, including drug-coated balloons, by Charité University Hospital, Berlin. Prof Speck receives research support from B. Braun; he is also serving as a consultant to Bayer-Schering AG, Berlin. Prof Scheller and Dr Cremers receive insignificant lecture fees from B. Braun. Dr Unverdorben has become an employee of B. Braun USA after finishing the trial.
Alfonso F, Pérez-Vizcayno MJ, Hernández R, Bethencourt A, Martí V, López-Mínguez JR, Angel J, Iñiguez A, Morís C, Cequier A, Sabaté M, Escaned J, Jiménez-Quevedo P, Bañuelos C, Suárez A, Macaya C, RIBS-II investigators. Long-term clinical benefit of sirolimus-eluting stents in patients with in-stent restenosis results of the RIBS-II (Restenosis Intra-stent: Balloon angioplasty vs. elective sirolimus-eluting Stenting) study. J Am Coll Cardiol. 2008; 52: 1621–1627.
Unverdorben M, Vallbracht C, Cremers B, Heuer H, Hengstenberg C, Maikowski C, Werner GS, Antoni D, Kleber FX, Bocksch W, Leschke M, Ackermann H, Boxberger M, Speck U, Degenhardt R, Scheller B. Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis. Circulation. 2009; 119: 2986–2994.