Sirolimus-Eluting Stent for Complex Lesions:Treatment of Saphenous Vein Graft Disease

It is estimated that 40% of saphenous vein grafts (SVG) are occluded and a higher number develop significant stenosis within 10 years after operation.¹ Our treatment options have been limited and disappointing. When treated with conventional percutaneous revascularization procedures, these lesions have a high incidence of subacute stent thrombosis, restenosis, and distal embolization. ² The First-In-Man (FIM) study and the multicenter, randomized trials, RAVEL and SIRIUS, reported minimal if any restenosis in native coronary arteries treated with sirolimus-eluting stents. ^3-5 The virtual lack of neointimal proliferation following the implantation of sirolimus-eluting stents may provide a new hope for the problem of SVG disease. The case presented in this article illustrates the potential of this novel technology for the treatment of recurrent SVG disease in a high-risk elderly, diabetic patient who has failed brachytherapy. Case Report A 79-year-old male with a history of hypertension, diabetes mellitus and hypercholesterolemia was referred to our hospital for implantation of a sirolimus-eluting stent in a previously stented, degenerated SVG. The patient underwent 4-vessel bypass grafting in 1980. In April 2001, he presented with unstable angina. At that time, coronary angiography revealed all native vessels to be occluded, with a patent internal mammary artery to the left anterior descending artery (IMA-LAD), SVG to Left Circumflex occluded, SVG-posterior lateral branch with moderated disease, and 95% obstruction in the proximal segment of the SVG-right coronary artery (RCA). The SVG-RCA obstruction was treated with a 3.5 x 18mm NIR Royale stent (Boston Scientific, Maple Grove, MN). Three months later, he presented with recurrent restenosis and was treated in August 2001 with a Cutting Balloon (Boston Scientific). In October 2001, he had another episode of restenosis accompanied by chest pain and underwent beta-radiation therapy. In February 2002 (4 months after radiation therapy), the patient developed proliferative in-stent restenosis and underwent another angioplasty with a Cutting Balloon. In June 2002, the patient experienced his fourth episode of restenosis in a period of 14 months and presented to the hospital with unstable angina. The patient was a poor candidate for redo CABG, and had already failed conventional PCI and brachytherapy. Thus, he was accepted for compassionate treatment with a sirolimus-eluting stent, according to the SECURE (Compassionate Use of Sirolimus-Eluting Stent) protocol. Informed, written consent was obtained. The graft was engaged using a 6Fr Judkins Right-4 guide catheter. Angiography showed an 80% stenosis in-stent and distal to the stent edge in the proximal-mid portion of the SVG-RAC graft (Figure 1). After crossing the lesion with a 0.014in wire, pre-interventional IVUS was performed, revealing severe proliferative intimal hyperplasia extending beyond the distal end of the stent. A 3.5 x 18mm sirolimus-eluting stent was deployed directly, without predilatation (Figure 1), and inflated up to 16 ATM. Post-intervention intravascular ultrasound (IVUS) interrogation revealed a well-expanded and apposed stent. The patient tolerated the procedure well, with no elevation in post-procedure cardiac enzymes. He was discharged on clopidogrel 75mg/day and aspirin 325 mg per day for an indefinite period, per the SECURE protocol. At 8-month follow-up, the patient remained asymptomatic. Repeat angiography was performed according to the study protocol. There was virtually no intimal proliferation inside the sirolimus-eluting stent or at the edge segments as revealed by both angiography and intravascular ultrasound (Figure 2). Discussion We describe a successful treatment of recurrent SVG restenosis with the use of a sirolimus-eluting stent. The patient had 4 episodes of symptomatic restenosis within a 24-month period. Late loss is the angiographic surrogate for neointimal proliferation after stenting and it was remarkable to observe an almost absence of late loss (Figure 2) 8 months after the implantation of the sirolimus-eluting stent. The treatment of degenerated saphenous vein grafts remains a challenge. Repeat bypass surgery is technically demanding with increased risk for complications. ⁶ Similarly, interventional techniques have provided unsatisfactory results when applied to SVG. The main limitations of the percutaneous approaches are higher rates of periprocedural myocardial infarction and enhanced intimal proliferation. In the Saphenous Vein Graft De Novo Study (SAVED) trial, conventional stents provided superior clinical outcomes as compared to balloon angioplasty, in spite of a similar high incidence of angiographic restenosis in both groups. ² Recent clinical trials have shown a striking reduction in neointimal proliferation after the implantation of sirolimus-eluting stents in native coronary arteries. While the First-In Man (FIM) and Randomized Study with the Sirolimus-eluting Velocity Balloon Expandable Stent (RAVEL) trials involved somewhat benign populations with short lesions treated with single stents, the Sirolimus-Coated Velocity Stent in Treatment of Patients with de novo Coronary Artery Lesions (SIRIUS) study included higher-risk patients and allowed the implantation of multiple stents to treat lesions that varied from 15 to 30mm in length. ^3-5 More recently, sirolimus-eluting stents have shown promising results in the treatment of in-stent restenosis. ⁷ None of these studies, however, included patients with SVG lesions. Whether sirolimus-eluting stents may alter our future approach to the treatment of SVG disease remains to be demonstrated in randomized clinical trials, but the present report illustrates the ability of this drug-eluting stent to tackle a very high-risk SVG lesion, which has already failed multiple interventional procedures, including brachytherapy. Patients with SVG lesions have been enrolled into the SECURE registry, ⁸ which will provide further insights into the utility of sirolimus-eluting stents for high-risk, recurrent SVG disease. It is nevertheless important to notice that the excellent clinical outcome observed in the present case does not rule out the possibility of late thrombotic complications when treating previously irradiated vessels using a sirolimus-eluting stent or any other type of stents. ⁹ Thus, one must consider indefinite use of combined anti-platelet therapy (aspirin and clopidogrel) when re-stenting previously irradiated vessels. In non-irradiated vessels, the use of clopidogrel for only 2 months after implantation of sirolimus-eluting stents has been shown to be safe and effective. Technical Considerations When dealing with complex lesions such as the present case, some technical aspects of drug-eluting stent deployment should be taken into account in order to maximize the effect of this unique anti-restenosis therapy. Vessel trauma outside the stented segment and gaps between stents, generally operator-dependent factors, may jeopardize the anti-restenotic effects of drug-eluting stents. In the present case, direct stenting was preferred to avoid potential balloon trauma during pre-dilatation. If pre-dilatation is performed, the balloon should always be shorter than the stent length. Preferably single balloon inflation should be used, with diligent balloon positioning and recording. All efforts should be made to cover the entire traumatized segment with the drug-eluting stent to avoid the risk of geographic miss. ¹⁰ This is because injured segments outside the stented zone do not benefit from the anti-proliferative effects of sirolimus. Similarly, since complete lesion coverage is of paramount importance, longer is better when selecting drug-eluting stents. Proper stent sizing in terms of stent diameter is also a crucial step during drug-eluting stent placement. Oversized and undersized drug-eluting stents may induce axial geographical miss, insufficient local drug concentration or disproportionate vessel trauma that may lead to inadequate inhibition of intimal hyperplasia. Oversized stents may cause unnecessary, extensive trauma to the adventitia and surrounding tissues, and consequently exaggerated neointimal proliferation. Probably the bigger is better strategy is no longer valid for sirolimus-eluting stents because late loss is insignificant. On the other hand, stents that are too small may provide insufficient drug concentrations due to either incomplete stent apposition, with a lack of contact between the stent struts and the vessel wall, or overexpansion of the stent cells and an increased space between the stent struts. The use of intravascular ultrasound in the present study was useful in determining stent size, and confirming stent apposition and complete coverage of the lesion. It is unlikely, however, that IVUS will be used to guide drug-eluting stent placement in routine clinical practice because of economic constraints. Alternatively, diligent angiographic assessment of vessel size and lesion location with the use of anatomical landmarks, such as side branches or guide wires with radiopaque markers, should be used to assure proper stent sizing and complete lesion coverage.

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