Drug-eluting stents (DES) have been established as a safe and effective tool in preventing in-stent restenosis and repeat revascularization in selected patients and lesions.^1,2 However, individual and procedure-related factors can reduce their inhibitory effect on neointimal hyperplasia.^3–5 Moreover, it has been shown that plaque morphology can affect not only the immediate stent implantation result,⁶ but even the mid- to long-term outcomes. This can occur by means of plaque prolapse, nonuniform strut and drug distribution,⁷ or exuberant neointimal hyperplasia. Unfortunately, currently available stent platforms may not perform optimally in cases of large plaque burden (such as in-stent restenosis)^8–10 or in vessels rich in elastic media (such as aorto-ostial lesions).¹¹ Thus, in such high-risk lesions, further strategies to limit or avoid restenosis are required.
We describe a novel approach to treat selected lesions at high risk of restenosis when there is a suboptimal result following initial stenting secondary to plaque prolapse. The “sandwich” technique consists of the simultaneous implantation of two fully overlapping DES in the same target lesion.
The hypothesis is that a double layer of drug-eluting stent struts might maximize plaque scaffolding while increasing local delivery of the antirestenotic agent.

Methods
Patient selection. Patients with significant coronary stenosis considered at high risk for recurrence were included in this series. Patients were considered to be at high risk of restenosis if any of the following criteria were present: ostial location in a vessel 3.5 mm or larger, severe plaque prolapse, multiple previous episodes of in-stent restenosis (including previous DES restenosis), 1 mm or more mismatch between stent size and visual estimated vessel size (usually similar to final balloon size).
Procedure. The technique was carried out as follows: after vessel wiring and predilatation (whenever appropriate), 2 DES of identical size and length were implanted one inside the other with almost complete overlap in a two-step procedure. All the patients were pretreated with aspirin, a thienopyridine and intravenous heparin. Following the index procedure, at least 100 mg daily of aspirin, and clopidogrel 75 mg a day or ticlopidine 250 mg twice a day (2 cases), were prescribed to all patients for at least 6 months. In 6 cases, a conventional balloon was used, while in 3 cases, the lesion was prepared with a cutting balloon; in 1 lesion, directional atherectomy was performed with a suboptimal result. Two fully overlapping DES were then implanted, one after the other in a sandwich fashion. Implanted stents had diameters in the 2.5 to 3.5 mm range. High-pressure post-dilatation (15–28 atm) after the second stent implantation was performed in 7 cases to optimize the angiographic result (with a noncompliant balloon in 2 cases).
Coronary angiograms were analyzed using a validated edge detection system (CMS, version 5.2, MEDIS, The Netherlands). Minimal lumen diameter (MLD), reference vessel diameter (RVD) and percent diameter stenosis at baseline, post-first stent implantation, post-second stent implantation and at follow-up were measured, respectively. Acute gain was defined as the difference between the MLD immediately after the procedure and the baseline. Angiographic restenosis was defined as diameter stenosis greater than or equal to 50% by quantitative coronary angiography (Figure 1: baseline; Figure 2: post-first stent implantation; Figure 3: post-second stent implantation and post-dilatation; Figure 4: angiographic follow-up).
Endpoints and analysis. The endpoints were technical feasibility assessed by means of angiographic success and procedural success, the early (30-day) rate of major adverse cardiovascular events (MACE) defined as death, myocardial infarction or target lesion revascularization (TLR). At 9 months, all patients were evaluated for the occurrence of MACE, restenosis and measurement of QCA parameters.

Results
From July 2002 until November 2004, we enrolled 10 patients with lesions considered at very high risk for restenosis. Specifically, double DES were implanted for the following reasons: (1) in 7 patients because the target lesion was an ostial lesion on a vessel 3.5 mm or larger (5 of them had an in-stent restenosis); (2) in 2 patients because of 2 or more events of in-stent restenosis, including one DES restenosis; (3) and in 1 patient because of severe plaque prolapse following implantation of the first DES (Table 1).
Angiographic success was achieved in all cases. In-hospital and 1-month outcomes were similarly uneventful. A scheduled angiographic control was performed after 4–6 months (at an earlier time if clinically suggested) in 10 (100%) of the cases. At long-term follow-up (mean 10.1 ± 1.8 months), there were no deaths, myocardial infarctions, or stent thromboses; TLR was carried out in 3 cases (30%) due to restenosis.
Angiographic analysis showed that minimum lumen diameter (MLD) changed from 0.89 ± 0.26 mm preprocedure, to 2.78 ± 0.7 mm after initial stent implantation, with a subsequent increase to 3.15 ± 0.61 mm after implantation of the second stent and post-dilatation (p < 0.001). At follow-up, MLD was 2.25 ± 1.49 (Figure 5). Angiographic restenosis occurred in 3 patients (30%), in 2 of them as focal restenosis, and in the other as a total occlusion at the ostium of a saphenous vein graft 50 mm proximal to the stent, and without any adverse clinical events. Of note, at angiographic follow-up, there was no evidence of aneurysmal dilatation.

Discussion
The present study reports a case series of patients with very high-risk lesions treated with a novel DES implantation technique, the “sandwich”. Our study suggests that this approach is feasible and safe in selected lesions. This technique may provide an alternative solution in a subset of lesions for which more traditional strategies have failed. Indeed, the sandwich technique, by means of implanting two DES, one inside the other, may be considered an additional interventional strategy to provide greater lesion scaffolding, better strut distribution and increased drug concentration and delivery, with a more effective mechanical and antiproliferative effect.
Drug-eluting stents have significantly reduced the frequency of in-stent restenosis and TLR in selected patients and lesions. However, most of the results obtained with DES have involved relatively simple lesions. High-risk lesions such as multiple ISR including DES restenosis or patients with a high-risk profile, such as patients on dialysis, may pose an unsolvable clinical problem. In addition, the occasional suboptimal result due to plaque prolapse following DES implantation may require an alternative treatment approach. Ratib et al. have also reported a case of DES implantation followed acutely by in-DES implantation of a bare-metal stent for stent recoil, but no follow-up of this single patient experience was reported.¹² Despite the fact that this experience is limited to 10 patients, it is comforting to know that no cases of stent thrombosis occurred, thus an initial and preliminary statement about the safety of this approach can be made.
Given the double strut layer and the risk for limited side branch access or branch compromise, bifurcation lesions are probably a relative contraindication to the sandwich approach, and a small increase in the risk of non-Q wave myocardial infarction can be anticipated in vessels with high plaque burden due to the potential for small branch closure.
In addition, we must remember that despite the favorable safety profile of the sandwich in this study, a number of reports have suggested that the risk of stent thrombosis might increase with DES, both acutely and long-term.¹³ Such risk may be higher in lesions treated with the sandwich, given the double metallic strut layer, the potential for stent underexpansion, and the higher drug dosage that may impair prompt endothelialization. In view of this risk, it is prudent to prescribe double antiplatelet therapy for at least 6 months in patients treated with the sandwich and to utilize this approach in large vessels where the metal-to-artery ratio will still be kept at low values.

Conclusion
This study provides the first technical description and early- and mid-term results of a novel double DES implantation technique for high-risk patients and lesions.