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Abstract & Commentary
Synopsis: In terms of the primary objective of the study, PTCA produced a significantly better long-term outcome than ROTA followed by adjunctive low-pressure PTCA.
Source: vom Dahl J, et al. Circulation. 2002;105: 583-588.
Despite improved long-term outcomes of per-cutaneous coronary intervention (PCI) in patients receiving coronary stents, in-stent restenosis (ISR) remains a significant problem despite optimal patient and lesion selection, adjuvant pharmacotherapy, and implantation techniques. The pathophysiology of restenosis in the stented patient is unique, the hallmark being intense cellular proliferation and neointimal formation, as opposed to vascular recoil and adverse remodeling. For this reason, the concept of atheroablation, as is performed with rotational atherectomy, is an appealing strategy in the approach to ISR. Previously published single-center trials have suggested that this technique can be performed safely and may result in reduction of angina and need for repeat revascularization. Therefore, vom Dahl and colleagues designed the Angioplasty Versus Rotational Atherectomy for In-Stent restenosis Trial (ARTIST), a multicenter, randomized study to assess whether rotational atherectomy with adjuvant low pressure balloon inflation (ROTA) was superior to angioplasty alone (PTCA) in patients with diffuse ISR.
Eligible patients demonstrated angina or objective evidence of ischemia in the target vessel distribution, as well as documented evidence of ISR, with > 70% stenosis in a 10-50 mm long segment, confined to within 5 mm of the edges of a previously deployed stent > 2.5 mm in diameter. Patients were randomized to receive either ROTA or PTCA. ROTA was preformed using a stepped-burr approach with a target burr-to-artery ratio of = 0.7, and was followed by angioplasty using an oversized balloon (0.25-0.5 mm larger than was used for stent implantation) inflated to low pressure (< 6 atmospheres [atm]). Additional balloon inflations to higher pressures were allowed at the operator’s discretion for suboptimal angiographic results. PTCA was performed according to the operator’s discretion and usual practice. Use of intravascular ultrasound (IVUS) was mandated only in 86 patients entered into an IVUS substudy, and was otherwise performed at the operator’s discretion. In both groups, glycoprotein IIb-IIIa inhibitor use and additional stent implantation were discouraged. Patients requiring additional stents due to suboptimal angiographic result were considered "procedural failures" and excluded from further analysis. The primary end point was minimal luminal diameter (MLD) at 6 months, as assessed by quantitative coronary angiography (QCA). Secondary end points were procedural success (efficacy), in-hospital complications (safety), restenosis (> 50% diameter stenosis) at 6 months and survival free of major adverse cardiac events (MACE), defined as death, myocardial infarction (MI), or need for repeat target vessel revascularization, at 6 months of follow-up.
In this study, 282 patients were entered into the trial. Of these, 146 underwent PTCA and 152 received ROTA. There were no significant differences between the groups in terms of clinical characteristics, or baseline stent or lesion characteristics. There were no differences between the groups with regard to procedural success. In both groups the major reason for procedural failure was the need for additional stent implantation, and these patients (15 in PTCA group and 10 in ROTA group) were excluded from further follow-up. There were significant differences in procedural characteristics, in large part mandated by the protocol outlined for ROTA. Most notably, patients receiving PTCA were treated with higher balloon inflation pressures (maximum of 12.7 ± 3.3 atm vs 6.1 ± 3.3 atm, P < 0.0001), with a much higher percentage treated with high-pressure (> 10 atm) balloon inflation (68.5% vs 7.2%; P < 0.0001). There were no differences between the groups in post-treatment MLD or short-term gain as measured by QCA. The patients receiving ROTA experienced higher complication rates during the index hospitalization (13.8% vs 7.5%), though this difference was not statistically significant. The primary end point, net gain in MLD by QCA at 6 months, was better in the PTCA group. The PTCA group demonstrated larger MLD (1.20 ± 0.56 mm vs 0.99 ± 0.62 mm; P = 0.008), lower residual stenosis (55.7 ± 19.9 vs 63.6 ± 22.3; P = 0.005). This translated into lower angiographic restenosis (= 50% diameter stenosis) rates (51.2% vs 64.8%; P = 0.039) for patients treated with PTCA. In addition, survival free of MACE at 6 months was higher after PTCA than after ROTA (91.3% vs 79.6%; P = 0.0052).
The IVUS substudy included 45 patients receiving PTCA and 41 patients receiving ROTA. Postprocedure IVUS evaluation demonstrated larger neointimal area in the PTCA group due to absence of debulking, but also larger minimal stent cross sectional area (CSA), an effect that is likely attributable to higher balloon inflation pressures. These combined to generate a larger minimal lumen cross sectional area (CSA) in the PTCA group than in the ROTA group at the end of the interventional procedure. In follow-up, the differences in stent CSA persisted, but the larger volume of neointima in the PTCA group resulted in equivalent minimal lumen CSA between the 2 groups at 6 months.
In contrast to previously published reports, results from the ARTIST trial would suggest that, while both groups experienced high "re-restenosis" rates, conventional PTCA resulted in superior angiographic and clinical outcomes when compared with rotational atherectomy for the treatment of ISR. Despite reduced amounts of neointima both immediately postprocedure and at follow-up angiography 6 months later, patients treated with rotational atherectomy performed according to this protocol, had higher rates of angiographic restenosis and MACE. The differences in adverse clinical events (8.9% in the PTCA group and 20.4% in the ROTA group) are intriguing, but the actual numbers of death or MI are not reported here. The difference in MACE does not appear to be driven exclusively by differences in need for repeat revascularization as it is in many clinical trials of restenosis. In fact, the need for target lesion revascularization was equivalent, 31% (45/146) in the PTCA group and 39% (60/152) in the ROTA group (P = NS). Of additional concern, there were more total occlusions in the ROTA group than in the PTCA group at follow up (7% vs 1%; P = "significant"). Thus, this study would suggest that rotational atherectomy with low pressure balloon inflation is probably not the procedure of choice for every patient with ISR.
As vom Dahl et al point out, the IVUS substudy, while small, may help to shed some light on the overall results of ARTIST. IVUS evaluation after intervention revealed larger-stent CSA in the PTCA treated group, suggesting that higher inflation pressure likely resulted in better stent expansion and apposition. Of note, this difference was not evident angiographically, as post-treatment MLD and short-term gain were equivalent between the two groups when evaluated by QCA. The larger stent CSA in the PTCA group, as demonstrated by IVUS, appears to have resulted in a better ability to accommodate subsequent neointimal proliferation during follow-up, despite the absence of debulking at the time of intervention. This would suggest that a significant proportion of stents were not optimally deployed both at baseline and after intervention, in the absence of additional high-pressure balloon inflations, despite apparently adequate angiographic results. As vom Dahl et al point out, this may explain why preliminary data from the ROSTER trial suggest a more favorable outcome with ROTA, as patients with inadequate stent expansion by IVUS were excluded from this study.
With the currently available stents and delivery systems, stent implantation has become much easier, faster and more forgiving than in the early days with the original Palmaz-Schatz stent, but technique is still important. Several currently available stent-delivery systems are marketed by their manufacturers as being adequate to obviate the need for additional high-pressure postdilitation after implantation, despite the fact that the balloons in question are compliant. To make matters worse, inadequate stent deployment may be present even with what appears to be a beautiful angiographic result. The ARTIST trial suggests that rotational atherectomy is not the single answer for approaching patients with ISR. As in Europe, IVUS is not uniformly available and is even less widely used in interventional laboratories in the United States, despite its clinical use. For operators who have the capability, IVUS is likely to be highly instructive in designing an approach to a given patient with in-stent restenosis. For those who do not, perhaps rotational atherectomy should be followed by high-pressure balloon inflation.
In-stent restenosis remains the most significant limitation to long-term success of PCI procedures. In terms of treatment of ISR, brachytherapy has shown much promise but is logistically difficult to administer and therefore not widely available. Coated stents hold out real promise of reduced ISR rates by inhibiting neointimal proliferation, and when clinically available are likely to have a positive effect on this disease process. However, all in-stent restenosis is not created equal. The problem of inadequate stent expansion cannot be overcome by any amount of tissue ablation or even prevention of neointimal formation, be it by rotational atherectomy, intracoronary brachytherapy, or even the use of a coated stent.
Dr. Vernon is Assistant Professor of Medicine, Director, VAMC Cardiac Catheterization Laboratory, University of New Mexico, Health Sciences Center, Albuquerque, NM.
1. Sharma SK, et al. J Am Coll Cardiol. 2001;37:55A.