Author + information
- Masaki Awata, MD,
- Shinsuke Nanto, MD, PhD, FACC⁎ (, )
- Masaaki Uematsu, MD, PhD, FACC,
- Takakazu Morozumi, MD, PhD,
- Tetsuya Watanabe, MD, PhD,
- Toshinari Onishi, MD,
- Osamu Iida, MD,
- Fusako Sera, MD,
- Jun-ichi Kotani, MD, PhD, FACC,
- Masatsugu Hori, MD, PhD, FACC and
- Seiki Nagata, MD, PhD
- ↵⁎Cardiovascular Division, Kansai Rosai Hospital, 3-1-69 Inabaso, Amagasaki, 660-8511, Japan
Drug-eluting stents (DES) have demonstrated reduced late loss (LL) and low target lesion revascularization (TLR) rates through an inhibitory effect on neointimal hyperplasia but might have a risk of late or very late stent thrombosis due to incomplete neointimal coverage (NIC) (1–3). A zotarolimus-eluting stent (ZES) (Endeavor, Medtronic, Minneapolis, Minnesota) is a next-generation DES that shows higher LL than a sirolimus-eluting stent (SES) (Cypher, Cordis, Miami, Florida), while demonstrating favorable inhibitory effects on TLR. We hypothesize the differences in LL will be reflected in different healing processes and might in part explain observed differences in safety. With angioscopy, we investigated the lumen/stent surfaces after placement of ZES for de novo lesions of the native coronary arteries and compared the findings with SES.
We investigated 30 DES implanted in 28 patients (21 men, age range from 43 to 83 years old) who suffered from stable angina pectoris, fulfilled the matching criteria, and agreed to receive follow-up angioscopy as well as angiography. Eighteen ZES were implanted in 18 consecutive patients who fulfilled the matching criteria. Follow-up angiography was performed approximately 8 months after stent implantation in all patients, and 14 of these patients (14 stents) agreed to receive follow-up angioscopy. These angioscopic findings were compared with the pooled data of 16 SES in 14 consecutive patients who also fulfilled the matching criteria. These patients all agreed to receive follow-up angioscopy 8 months after implantation. Matching criteria included: 1) de novo lesion of >50% diameter stenosis, which caused myocardial ischemia; 2) native coronary artery of 2.25 to 3.5 mm diameter; 3) nonacute coronary syndrome culprit lesions; and 4) total stented length <47 mm. All patients were taking aspirin 100 to 200 mg/day. Ticlopidine 200 mg/day was additionally given for at least 3 months. Neither glycoprotein IIb/IIIa inhibitors nor clopidogrel was used, because they were not approved for clinical use in Japan at the time of this study. The medical ethics committee at Kansai Rosai Hospital approved the study, and all patients gave written informed consent.
The NIC was angioscopically classified into 4 grades (Fig. 1)as previously described (1,2). In brief, grade 0: stent struts were exposed; grade 1: struts bulged into the lumen, although they were covered; grade 2: struts were embedded but were seen translucently; and grade 3: struts were fully embedded and invisible. If NIC was heterogeneous, the dominant pattern was adopted. All results are expressed as mean ± SD unless otherwise stated. Comparisons between the 2 groups were done with the Wilcoxon rank sum test. Categorical variables were analyzed with the Fisher exact test for 2 × 2 comparisons; for more than 2 × 2 comparisons, the chi-square test was used. Statistical significance was defined as p < 0.05.
Patient, lesion, and procedure characteristics were equally distributed between ZES and SES. Implanted stent diameter was 3.22 ± 0.31 mm in SES versus 3.04 ± 0.41 mm in ZES (p = 0.22); stent length was 22.7 ± 3.40 mm in SES versus 21.9 ± 4.47 mm in ZES (p = 0.97). Although SES had a trend toward smaller reference diameters than ZES (2.89 ± 0.40 mm in SES vs. 3.22 ± 0.74 mm in ZES, p = 0.23), baseline angiogram showed no statistical differences. Although the minimal lumen diameter after procedure also tended to be smaller in SES (2.70 ± 0.34 mm in SES vs. 3.02 ± 0.51 mm in ZES, p = 0.08), in-stent LL from post-procedure to follow-up was smaller in SES (0.07 ± 0.18 mm in SES vs. 0.51 ± 0.17 mm in ZES, p < 0.0001), reaching the similar minimal lumen diameter and percent diameter stenosis at follow-up. None of the lesions showed restenosis.
The ZES showed greater NIC grades than SES (p = 0.0004, chi-square test) (Figs. 1 and 2).⇓Thrombi tended to be more frequent in SES (31%) than in ZES (7%, p = 0.2, Fisher exact test). All thrombi were mural, subclinical, and associated with sites with grade 0 or 1. A red thrombus was detected in a ZES at a grade 1 site, although the dominant grade was grade 2. Yellow plaques (YP) were detected in 2 ZES versus in 11 SES (p = 0.004, Fisher exact test), which were all detected underneath the neointima at sites showing grades 0 to 2 coverage.
This study is the first to compare the 2 different platforms of DES with angioscopy. In contrast to SES, ZES had NIC similar to what we had seen previously in bare-metal stents (BMS) (2). The frequency of mural thrombus tended to be lower and YP were less frequently visible in ZES than in SES.
A DES platform with extremely limited LL and low restenosis rates might have a risk of incomplete NIC and subsequent late or very late stent thrombosis. Whereas ZES showed a greater in-stent LL than SES, the majority of ZES showed complete NIC similar to BMS (2). Angioscopic grade 0/1 coverage might be a consequence of delayed endothelialization. An animal study demonstrated that the extent of stent coverage by endothelial cells was greater with ZES, with almost complete coverage, than with SES at 21 days after the placement in the rabbit iliac arteries (4). All thrombi observed in this study were found at grade 0/1 sites; the dominant pattern in ZES-implanted vessels in this study was grade 2/3 with less adhesion of thrombus. The ZES-implanted vessels were associated with significantly less yellow plaques than SES. Yellow plaque is also reduced by BMS placement, because both the stent and the YP underneath the stent are covered by neointimal development (5). The ZES is likely to have a “sealing” effect, because ZES shows NIC more like that of BMS. These angioscopic findings suggest that arterial endothelial healing of ZES at 8 months after stent placement was more competent than SES. In general, mean in-stent LL below 0.65 mm with stent platforms is associated with TLR rates below 10% (6). Considering the risk of stent thrombosis due to incomplete NIC, it is preferable for DES to have sufficient neointimal volume no greater than LL of 0.65 mm.
Although the single-center, nonrandomized, matched-control, and observational nature with a small sample size of this study should be noted as a limitation, this study suggests that arterial endothelial healing after stenting is more competent in ZES than in SES. Optimal LL might be desirable for adequate arterial endothelial healing after stenting.
Please note: This research was supported by a research grant to Dr. Awata from the Japan Labour Health and Welfare Organization.
- American College of Cardiology Foundation
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