Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - 31st Annual Congress of the European Society of Cardiology

Barcelona, Spain / August 29-September 2, 2009

As confirmed here at the ESC, current stents offer predictable efficacy and safety at least over the short term. In an update from the ISAR (Intracoronary Stenting and Angiographic Results) Left Main study, which compared sirolimus- to paclitaxel-eluting stents in 607 patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention (PCI), follow-up has now reached three years. Consistent with the one-year results reported previously, both stents were associated with similarly low rates of death, myocardial infarction (MI) and target lesion revascularization (TLR) as well as secondary clinical and angiographic outcomes.

Similarly, new data from a large German registry found both types of drug-eluting stent (DES) to be superior to bare metal stents (BMS) but comparable to each other. “The efficacy and safety of sirolimus- and paclitaxel-eluting stents have generally been comparable with respect to the prevention of clinically relevant restenosis,” reported Dr. Miroslav Ferenc, Herz-Zentrum Bad Krozingen, Germany. Although he did present evidence from a consecutive cohort registry that these devices might not be interchangeable for different indications, he noted that the preponderance of data suggest that differences, if any, in efficacy and safety over periods of one to three years are likely to be small. Differences beyond this point are still being evaluated.

Side-branch Stent Outcomes

The new data from the German cohort were generated by the 309 consecutive patients in the 701-patient series who received a side-branch stent. The ratio of sirolimus- to paclitaxel-eluting stents in this series was nearly 2:1 even though the baseline characteristics were similar. At the end of three years of follow-up, the unadjusted rates of death, although lower in the group receiving the sirolimus-eluting stent, did not differ significantly (6.49% vs. 10.55%; P=0.19). However, the hazard ratio (HR) adjusted for risk did find a significantly greater risk of death in the paclitaxel-eluting stent group (HR 2.45; 95% CI, 1.05-5.73; P=0.039). Other outcomes, including TLR and MI, were less common but not statistically different in patients receiving the sirolimus stent relative to the paclitaxel stent.

“In left main lesions, our cohort suggests that paclitaxel-eluting and sirolimus-eluting stents offer similar efficacy, but the sirolimus-eluting stent appears to be superior for long-term outcome if a stent needs to placed in a side branch,” concluded Dr. Ferenc.

Left Main Disease: A Registry Analysis

Despite the frequency with which stents offer similar results in large trials, there is increasing interest in the real-world experience generated by cohort series and registries. Such data may provide a better understanding of stent performance in unselected patients from the community setting. New data from several of these sources were presented here at the ESC, suggesting that the current stents are similar but not necessarily interchangeable even over relatively short periods of follow-up.

For example, a multinational Asian registry that included centres in Japan, Korea, Indonesia and Thailand documented procedural success in 100% and major adverse cardiovascular events (MACE) at 30 days in 0% of their registry of DES for left main disease. These included 248 patients receiving sirolimus-coated stents, 172 receiving paclitaxel-coated stents, 104 receiving zotarolimus-coated stents, 50 receiving everolimus-coated stents and 42 receiving a stent coated with endothelial progenitor cells (EPC).

However, TLR rates were more than twice as high on either the zotarolimus-coated stents or the EPC stents when compared to the sirolimus- or everolimus-coated stents at the end of nine months (14.3% vs. 6%; P<0.05 for each difference). Paclitaxel-eluting stents had a higher rate of TLR (8.7%) than the sirolimus- and everolimus-eluting stents but were not statistically different from either the best or the worst performing stents. According to Dr. Sunao Nakamura, New Tokyo Hospital, Chiba, Japan, restenosis rates at nine months produced the same pattern of significant differences. “This is not only true in the left main subgroup, but in several other important subgroups as well,” he confirmed, citing a very similar pattern of differences in which sirolimus and everolimus stents outperformed the other three types of DES in small artery disease and in patients with chronic total occlusion. Again, the advantage was statistically significant for these two types of stents over zotarolimus and EPC stents while numerically superior to paclitaxel-eluting stents.

Here at the ESC, Dr. Naoki Miyoshi, Department of Cardiology, University of Kobe, Japan, described a study in which 24 patients received a sirolimus- and a paclitaxel-eluting stent in the same artery. In 11 cases, the paclitaxel stent had the proximal position. In the remaining 13, the sirolimus-eluting stent was in the proximal position. When optical coherence tomography was performed six months after stent placement, neointimal thickness was greater but less uniform around the paclitaxel-eluting stent when compared to the sirolimus-eluting stent. Fewer struts were uncovered with the paclitaxel-eluting stent, but the positional relationship did not affect neointimal thickness.

“It is difficult to make any meaningful speculation about whether these differences are clinically relevant, but I think the important observation is that these stents are not the same,” remarked Dr. Miyoshi.

Reducing Restenosis Risk: Advances in Stent Design

Two of the most promising stent designs discussed here at the ESC employ a biodegradable polymer platform that attempts to reduce the risk of restenosis by diminishing foreign body exposure. One of these stents combines a biodegradable poly DL-lactide-co-glycolide (PLG) polymer with a reservoir technology designed to provide unidirectional delivery of sirolimus to the vessel wall. The other also employs a sirolimus coating without reservoir technology. The polymer in this second device is designed to erode within nine weeks.

In the most recent results from the first device generated by 394 patients in nine countries who were randomized to the biodegradable stent or to a paclitaxel-eluting stent, angiographic results have strongly favoured the biodegradable device. At 12 months, this included highly significant relative reductions of in-stent late loss (P<0.001), in-segment late loss (P<0.001), in-stent binary restenosis (P=0.002) and neointimal hyperplasia volume (P=0.004). The rates of in-hospital MACE at six months were not significant, but MACE outside of the hospital is approaching significance (P=0.08) favouring the biodegradable stent.

According to presenter Dr. Jean Fajadet, Clinique Pasteur, Toulouse, France, the data so far suggest that the biodegradable stent is outperforming the traditional stent, although he cautioned that longer follow-up is needed.

The second stent is being tested in 2603 patients in a randomization of 2:1:1 that includes a sirolimus- and an everolimus-eluting stent. The study, called ISAR-TEST4, is a non-inferiority trial with a primary end point of cardiac death, MI or TLR. So far, the stents have been comparable.

“The stents all performed about the same at the end of one year but this follow-up is probably too short to draw any final conclusions,” remarked Dr. Julinda Mehilli, Deutsches Herzzentrum, Munich, Germany. The primary end point was reached in 13.8% and 14.4% of the biodegradable and non-biodegradable stent groups, respectively, which did not differ significantly. She, like Dr. Fajadet, indicated that one of the most important advantages of stents with biodegradable polymers is a reduced risk of late stent thrombosis, making two- and three-year follow-ups important for confirming the superiority of this design.

Summary

Over the short term, the available evidence indicates that the most widely used DES stents have excellent short-term performance, but long-term follow-up suggests that performance diverges over time. Differences between devices have been observed across several indications, including left main disease and side branch arteries. While efforts to create the perfect stent continue with the current development of devices that use biodegradable polymers, selecting stents with the lowest TLR rates at three years will be increasingly recognized as important as selecting stents with low TLR rates at one year.