Sirolimus or Paclitaxel Drug-Eluting Stents for Treatment of Chronic Total Occlusions of Coronary Arteries: Much Ado about Very

Chronic total occlusions (CTO) represent about 10% of all coronary lesions treated by percutaneous interventions. They traditionally have posed significant problems for patients and operators, with both lower initial success rates and higher long term failure rates than other, nonoccluded, coronary lesions. Initial success requires overcoming the often daunting technical challenges of crossing the chronically occluded site. Even when this can be accomplished, the long-term results have been tarnished by higher rates of restenosis and reocclusion. Nevertheless, it was shown conclusively a few years ago that when the CTO can be crossed and treated, bare metal stents improved the success rates and reduced the long-term failure rates compared to balloon angioplasty (POBA). Restenosis was reduced from about 65–75% with POBA to 30–40% with bare metal stents. This otherwise remarkable improvement somehow seemed less thrilling compared to the more dramatic reductions in restenosis that occurred in nonoccluded lesions. And even as the technology of wires and catheters and the skills of operators improved, success rates in CTO remained stable and comparatively rather disappointing. That is, until the introduction of drug-eluting stents (DES). Development of a drug-eluting stent device that inhibits the neointimal proliferative processes that underlie restenosis has been a major achievement in coronary intervention. In conventional percutaneous coronary interventions of nonoccluded arteries, recurrence rates have fallen dramatically to a few percent. Presently, the discussion issues involve topics such as diabetes, small vessels, branch points, left main lesions, and so on. In all of these cases, the questions have been whether DES produces significantly better outcomes than bare metal stents or other treatments. Data are still being collected and interpreted, and one hopes that further guidance will emerge soon. It has also become reasonably clear that DES improve the outcomes in CTO. As with other specific anatomic groupings, data on this clinical subset are only now emerging, and we are still very much in the adolescent, immature phases of understanding the full and appropriate utility of DES in CTO. The earliest data that have been reported have been related to the sirolimus-eluting stents (SES) since they were the first ones available clinically. Reports from Hoye et al.,¹ Ge et al.,² and Nakamura et al.,³ indicate that SES in CTO are associated with freedom from adverse events over the long term (1 to 3 years) that ranges from 80–95%, compared to 40–80% with bare metal stents. Binary restenosis rates are reported in the range of 2–9% with SES, compared to about 30–35% with bare metal stents. Nevertheless, the number of patients who received SES in these reports are fewer than 250, and the number with angiographic follow up are fewer still, perhaps less than 150. Introduced into clinical practice more recently than the SES, the paclitaxel-eluting stent (PES) is now undergoing appropriate scrutiny. Its utility in CTO is one area of examination. There are two prior reports of PES in CTO, both by Werner et al.,^4,5 involving at most 100 patients, and probably fewer than that since there likely was overlap in reporting. Long-term freedom from adverse events with PES appears in these very small reports to be in the range of 80%, with binary restenosis rates of 8–10%. The current report by Jang et al.⁶ presented in this issue of the Journal involves 107 patients with CTO who received SES, and only 29 patients with CTO who received PES. Furthermore, this was a retrospective analysis of patients receiving routine clinical care. The restenosis rate at 6 months in the SES group was 9.4%, very much in line with other clinical reports, but the restenosis rate in the PES group was 28.6%. This value is quite high and quite anomalous compared to other reported values for restenosis. When coupled with the small sample size of 29 patients, the only conclusion that can be drawn is that this is too small a sample from which to draw meaningful conclusions. While a large, randomized trial would be needed in order to make a statistically significant comparison of SES vs. PES in the group of patients with CTO, this may never be able to be accomplished, and one wonders whether it ever should. Given the relative infrequency of CTO lesions, the duration of time over which the necessary number of patients would have to be recruited, the likely technical developments that would occur during that time (including new DES designs), and the likely inability to control for important clinical covariates, it appears that the question of which DES may be “better” in CTO may actually be unanswerable. Perhaps it would be better to spend time, energy and precious resources on other important topics. For example, the ability to cross and treat a CTO is still challenging and difficult, and more investigation is needed. For the time being, it appears that DES of whatever variety likely are equivalently good (equivalently great!) when they can be successfully placed in chronic total occlusions.

1. Hoye A, Tanabe K, Lemos PA, et al. Significant reduction in restenosis after the use of sirolimus-eluting stents in the treatment of chronic total occlusions. J Am Coll Cardiol 2004;43:1954–1958. 2. Ge L, Iakovou I, Cosgrave J, et al. Immediate and mid-term outcomes of sirolimus-eluting stent implanation for chronic total occlusions. Eur Heart J 2005;26:1056–1062. 3. Nakamura S, Muthusamy TS, Bae J-H, et al. Impact of sirolimus-eluting stent on the outcome of patients with chronic total occlusions. Am J Cardiol 2005;95:161–166. 4. Werner GS, Krack A, Schwarz G, et al. Prevention of lesion recurrence in chronic total coronary occlusions by paclitaxel-eluting stents. J Am Coll Cardiol 2004;44:2301–2306. 5. Werner GS, Schwarz G, Prochnau D, et al. Paclitaxel-eluting stents for the treatment of chronic total coronary occlusions: A strategy of extensive lesion coverage with drug-eluting stents. Cathet Cardiovasc Diagn 2006;67:1–9. 6. Jang SK, Hong M-K, Lee CW, et al. Comparison between sirolimus- and paclitaxel-eluting stents for the treatment of chronic total occlusions J Invasive Cardiology 2006;18:205–208.