Coated Stents for In-Stent Restenosis
Abstracts & Commentary
Synopsis: Sirolimus-eluting stents markedly reduce in-stent restenosis and clinical events over 1 year in patients with restenosis in conventional stents.
Sources: Sousa JE, et al. Circulation. 2003;107:24-27; Degertekin M. J Am Coll Cardiol. 2003;41:184-189.
Sirolimus-eluting stents (ses) have shown much promise in reducing restenosis rates when implanted in de novo coronary lesions. However, in 2003, treating in-stent restenosis (ISR) remains a significant challenge in clinical practice, and, at present, little is known about the potential effects of drug-eluting stents on the prevention of recurrent restenosis or on clinical outcomes of patients receiving them for ISR. Reports from 2 small, nonrandomized patient series published last month begin to shed some light on this issue and raise questions about the efficacy of this technology when applied beyond the patient population studied in clinical trials.
Sousa and colleagues present outcomes from a pilot study of 25 consecutive patients with ISR who were treated with £ 2 18-mm slow-release (> 28-day) sirolimus-eluting Bx VELOCITY stents. This series excluded patients with lesions > 36 mm in length, lesions in saphenous vein grafts, and patients previously treated with intravascular brachytherapy. All patients were successfully treated with 1 (n = 16) or 2 (n = 9) SES. Antiplatelet therapy consisted of aspirin (ASA) given at least 12 hours preprocedure and indefinitely postprocedure, as well as clopidogrel 300 mg immediately postprocedure and then 75 mg/d for 60 days. Follow-up consisted of clinical evaluation, quantitative coronary angiography (QCA), and intravascular ultrasound (IVUS) at 4 and 12 months. In-stent and in-lesion (5 mm proximal to and 5 mm distal to stent margins) segments were analyzed.
Of the patients studied, 80% were male, 24% were diabetic, and 20% had recurrent ISR. The treated lesion was classified as focal ( £ 10 mm) in 32%, diffuse intra-stent in 40%, and diffuse proliferative (involvement extending beyond stented segment) in 28%. Angiographic follow-up revealed only 1 patient with (asymptomatic) ISR. The remainder of patients demonstrated only minimal decrease (0.36 ± 0.46 mm) in in-stent minimal luminal diameter (MLD) and essentially no change (0.16 ± 0.42 mm) in in-lesion MLD at 12-months. IVUS follow-up revealed only minimal neointimal proliferation with percent volume obstruction of 0.81 ± 1.7 and 1.76 ± 3.44, at 4 and 12 months respectively. At 1 year, no clinical events, including recurrent angina, stent thrombosis, repeat revascularization, or major adverse cardiac events (MACE), defined as myocardial infarction (MI), stroke, or death, were reported.
Sousa et al conclude that, despite the limitations of a small, nonrandomized cohort of patients and the absence of a control group, the results of this study are encouraging given good angiographic, IVUS, and clinical outcomes demonstrated in this patient group. They point out that a longer period of follow-up coupled with larger randomized, controlled trials will be necessary to determine whether this approach will yield acceptable results or represent an acceptable alternative to brachytherapy in the treatment of ISR.
Degertekin and colleagues studied 16 patients with ISR in a native coronary artery (> 2.5 mm and < 3.5 mm in diameter) and objective evidence of ischemia. This series included 4 patients previously treated with brachytherapy. All patients were successfully treated with up to 5 SES. Antiplatelet therapy consisted of ASA and clopidogrel 300 mg immediately postprocedure and then 75 mg/day for 2-4 months at the discretion of the operator. Follow-up consisted of QCA and IVUS evaluation of in-stent and in-lesion segments at 4 months and clinical evaluation at 9 months.
In this series, 75% of patients were male and 25% were diabetic. Four patients (25%) had recurrent ISR after intracoronary brachytherapy. The treated lesion was classified as focal (£ 10 mm) in 3 patients, diffuse intra-stent in 5 (31.2%), diffuse proliferative in 5 (31.2%), and total occlusion in 3 (18.7%). Nine patients received a single SES, 6 received 2 SES (1 of these procedures was felt to be unsuccessful) and 1 received a total of 5 SES for treatment of a total occlusion. QCA and IVUS follow-up were completed in 15 patients. Angiography revealed 3 patients with recurrent ISR, all of which were asymptomatic. One patient demonstrated total occlusion at follow-up after an initially unsuccessful procedure due to failure to achieve adequate stent expansion. The second patient demonstrated a 59% in-lesion stenosis in a gap between 2 SESs, and the third patient, a heart transplant recipient, developed 62% stenosis proximal to the stented segment in an uncovered area of balloon injury. Overall QCA analysis revealed a minimal decrease in in-stent and in-lesion MLD at 4 months (0.26 ± 0.67 mm and 0.21 ± 0.62 mm, respectively). IVUS follow-up revealed minimal neointimal proliferation with percent volume obstruction of 1.1 ± 2.6 at 4 months. Clinical follow-up at 9 months revealed 2 deaths and 1 Q-wave MI. One patient died suddenly 3.5 months after successful implantation of 2 SES in the right coronary artery. The other death occurred in a patient who had failed brachytherapy and who did not show evidence of ISR at follow-up and who died of congestive heart failure 9 months after the index procedure. The MI occurred in the patient who received 5 SES 7 months after the index procedure. Of interest, angiography showed total vessel occlusion, which resolved with thrombus aspiration, and IVUS revealed no neointimal proliferation within the stented segment.
Degertekin et al discuss similar limitations of their small observational study, as well as the need for data from larger, randomized clinical trials. They point out that their series of patients presented with extremely complex lesions at high risk for adverse procedural and clinical outcomes, including those previously treated with brachytherapy and those with occlusive ISR. Despite this, procedural and in-hospital outcomes were uneventful and overall low rates of neointimal proliferation by IVUS follow-up at 4 months were encouraging. They acknowledge that 1 patient death and 1 MI can likely be attributed to thrombotic events, raising questions about how antithrombotic therapy should be handled in this clinical scenario. They also point out the importance of scrupulous technique and probably IVUS guidance, when SES use is extended to higher-risk patient populations, as 2 of the adverse outcomes in this series may be attributable to technical issues such as gaps between stents and unstented areas of balloon injury.
Comment by Sarah M. Vernon, MD
The first "coated stent," the Cordis/J & J Cypher (sirolimus-eluting Bx VELOCITY® stent) will likely be FDA-approved early in the second quarter of this year and is expected to be released for widespread clinical use immediately afterward. To say that this is a highly anticipated event in the interventional cardiology community would be an understatement. Based on the data from RAVEL and SIRIUS, expectations are high that drug-eluting stents will significantly impact outcomes, namely restenosis rates, of coronary stenting and start a "revolution" that will "forever change" interventional cardiology, as we know it. While all of this may eventually prove to be true, it’s probably somewhat premature to assume that coated stents will represent "the Holy Grail" for every patient, lesion subset, or indication that we encounter in clinical practice. These 2 recent reports of outcomes in patients receiving SES for ISR, though small and nonrandomized, are both encouraging and sobering. They remind us that we still have a lot to learn about what the imminent coated-stent technology will have to offer to patients in "real-life" clinical practice, many of whom, in this day and age, have very complex coronary artery disease indeed. We need to remember that we have good data about the efficacy of brachytherapy and extensive experience with CABG surgery, either of which may be a very acceptable strategy for a given patient with ISR. The remarkable results of RAVEL and SIRIUS should not be extrapolated to apply to many of the patients we encounter almost daily in clinical practice, not only those who already have ISR, but to those with ostial, calcified, total occlusion, bifurcation, or vein graft lesions to name a few. The "cat will be out of the bag" soon, and it’s likely to be a good thing for interventional cardiologists and their patients as a whole. However, a coated stent may not be the answer for every patient referred to the cardiac catheterization laboratory. As was the case when the first Palmaz-Schatz stent was released for clinical use almost a decade ago, we still have a lot left to learn about patient and lesion selection, so that we can achieve the best possible outcomes that coated-stent technology will have to offer.
Dr. Vernon is Assistant Professor of Medicine Director, VAMC Cardiac Catheterization Laboratory University of New Mexico Health Sciences Center, Albuquerque, NM.
Synopsis: Sirolimus-eluting stents markedly reduce in-stent restenosis and clinical events over 1 year in patients with restenosis in conventional stents.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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