As compared with a standard coronary stent, a sirolimus-eluting stent shows considerable promise for the prevention of neointimal proliferation, restenosis, and associated clinical events.

Background-The purpose of this study was to determine the efficacy of stent-based delivery of sirolimus (SRL) alone or in combination with dexamethasone (DEX) to reduce in-stent neointimal hyperplasia. SRL is a potent immunosuppressive agent that inhibits SMC proliferation by blocking cell cycle progression. Methods and Results-Stents were coated with a nonerodable polymer containing 185 g SRL, 350 g DEX, or 185 g SRL and 350 g DEX. Polymer biocompatibility studies in the porcine and canine models showed acceptable tissue response at 60 days. Forty-seven stents (metal, nϭ13; SRL, nϭ13; DEX, nϭ13; SRL and DEX, nϭ8) were implanted in the coronary arteries of 16 pigs. The tissue level of SRL was 97Ϯ13 ng/artery, with a stent content of 71Ϯ10 g at 3 days. At 7 days, proliferating cell nuclear antigen and retinoblastoma protein expression were reduced 60% and 50%, respectively, by the SRL stents. After 28 days, the mean neointimal area was 2.47Ϯ1.04 mm 2 for the SRL alone and 2.42Ϯ1.04 mm 2 for the combination of SRL and DEX compared with the metal (5.06Ϯ1.88 mm 2 , PϽ0.0001) or DEX-coated stents (4.31Ϯ3.21 mm 2 , PϽ0.001), resulting in a 50% reduction of percent in-stent stenosis. Conclusions-Stent-based delivery of SRL via a nonerodable polymer matrix is feasible and effectively reduces in-stent neointimal hyperplasia by inhibiting cellular proliferation.

Background-We have previously reported a virtual absence of neointimal hyperplasia 4 months after implantation of sirolimus-eluting stents. The aim of the present investigation was to determine whether these results are sustained over a period of 1 year. Methods and Results-Forty-five patients with de novo coronary disease were successfully treated with the implantation of a single sirolimus-eluting Bx VELOCITY stent in São Paulo, Brazil (nϭ30, 15 fast release [group I, GI] and 15 slow release [GII]) and Rotterdam, The Netherlands (15 slow release, GIII). Angiographic and volumetric intravascular ultrasound (IVUS) follow-up was obtained at 4 and 12 months (GI and GII) and 6 months (GIII). In-stent minimal lumen diameter and percent diameter stenosis remained essentially unchanged in all groups (at 12 months, GI and GII; at 6 months, GIII). Follow-up in-lesion minimal lumen diameter was 2.28 mm (GIII), 2.32 mm (GI), and 2.48 mm (GII). No patient approached the Ն50% diameter stenosis at 1 year by angiography or IVUS assessment, and no edge restenosis was observed. Neointimal hyperplasia, as detected by IVUS, was virtually absent at 6 months (2Ϯ5% obstruction volume, GIII) and at 12 months (GIϭ2Ϯ5% and GIIϭ2Ϯ3%). Key Words: angiography Ⅲ drugs Ⅲ stents Ⅲ restenosis Ⅲ ultrasonics D espite major technological advances in the past decades, of which the coronary stent is one of the most important, the percutaneous treatment of coronary artery disease is still hampered by a 20% to 30% incidence of restenosis. The list of candidate therapies and devices for prevention of restenosis after angioplasty is long and ever expanding. However, few if any have substantially improved the result of stenting for the treatment of de novo lesions. Intracoronary radiation has so far proven to be effective for the treatment of in-stent restenosis but not for the treatment of de novo lesions. 1 As a result of their ability to deliver prolonged and sufficient intramural drug concentrations to the target coronary segment, drug-eluting stents have emerged as a potential solution for restenosis. Our group has recently reported an almost complete absence of neointimal hyperplasia 4 months after implantation of sirolimus-eluting Bx VELOCITY stents. 2 The local release of sirolimus (rapamycin, Rapamune), a natural macrocyclic lactone with potent immunosuppressive action, 3 resulted in elimination of restenosis in this first series of patients. Comparable results have only been observed after the implantation of high-activity ␤-emitting stents (9 mm 3 of neointimal hyperplasia at 6-month follow-up). 4 However, a worrying late progression of in-stent neointimal hyperplasia was observed between 6 months and 1 year after implantation of radioactive stents. 5 Conclusions-This See p 1996The aim of the present investigation was to determine whether sirolimus-eluting stents produce a sustained suppression of the neointimal proliferation over a period of 1 year or merely delay the restenosis process. Methods Study PopulationForty-five patients with nati...

SRL-eluting stents favorably modulate neointimal formation for 30 days in the porcine coronary model. Long-term inhibition of neointimal hyperplasia is not sustained presumably due to delayed cellular proliferation despite increased levels of the cyclin-dependent kinase p27(kip1) in the vessel wall.

Background-The safety and efficacy of sirolimus-eluting stenting have been demonstrated, but the outcome of patients treated with this novel technology beyond the first year remains unknown. We sought to evaluate the angiographic, intravascular ultrasound (IVUS), and clinical outcomes of patients treated with sirolimus-eluting stents 2 years after implantation. Methods and Results-This study included 30 patients treated with sirolimus-eluting Bx Velocity stenting (slow release [SR], nϭ15, and fast release [FR], nϭ15) in São Paulo, Brazil. Twenty-eight patients underwent 2-year angiographic and IVUS follow-up. No deaths occurred during the study period. In-stent late loss was slightly greater in the FR group (0.28Ϯ0.4 mm) than in the SR group (Ϫ0. 09Ϯ0.23 mm, Pϭ0.007). No patient had in-stent restenosis. At 2-year follow-up, only 1 patient (FR group) had a 52% diameter stenosis within the lesion segment, which required repeat revascularization. The target-vessel revascularization rate for the entire cohort was 10% (3/30) at 2 years. All other patients had Յ35% diameter stenosis. Angiographic lumen loss at the stent edges was also minimal (in-lesion late loss was 0.33Ϯ0.42 mm [FR] and 0.13Ϯ0.29 mm [SR]). In-stent neointimal hyperplasia volume, as detected by IVUS, remained minimal after 2 years (FRϭ 9.90Ϯ9 mm 3 and SRϭ10.35Ϯ9.3 mm 3 ). Conclusions-This study demonstrates the safety and efficacy of sirolimus-eluting Bx Velocity stents 2 years after implantation in humans. In-stent lumen dimensions remained essentially unchanged at 2-year follow-up in the 2 groups, although angiographic lumen loss was slightly higher in the FR group. Restenosis "catch-up" was not found in our patient population. Key Words: stents Ⅲ angiography Ⅲ ultrasonics Ⅲ restenosis A new generation of drug-eluting coronary stents designed to limit restenosis has been developed recently. The clinical success of these novel technologies will depend on a complex interaction between stent, coating matrix, drug, and the vessel wall. Stents coated with sirolimus, a natural macrocyclic lactone with immunosuppressive and antiinflammatory action, represented the first successful attempt to abolish restenosis in human coronary arteries. 1-3 A virtual absence of neointimal proliferation was observed 1 year after implantation of sirolimus-eluting Bx Velocity stents in a pilot study. 2 Subsequently, the RAVEL (a RAndomized comparison of a sirolimus-eluting Bx VELocity stent with a standard stent for coronary revascularization) investigators reported an absence of both angiographic restenosis at 6 months and target-lesion revascularization 1 year after the implantation of sirolimus-eluting stents in a multicenter randomized trial. 3 Although encouraging, potential late side effects of these drug-eluting coronary stents may pose limitations. Lessons from intracoronary brachytherapy include the development of late thrombosis and neointimal proliferation that may occur beyond the first year after treatment. 4 -6 In the present study, we evaluated the clinical...

Background-Despite the proven superiority of sirolimus-eluting stents (SESs) compared with bare stents in the first year after implantation, long-term outcomes of patients treated with these novel devices remain unknown. Our goal was to evaluate the clinical, angiographic, and intravascular ultrasound (IVUS) outcomes of patients treated with SESs 4 years after implantation. Methods and Results-The study included 30 patients treated with sirolimus-eluting Bx Velocity stenting (slow release [SR; nϭ15] and fast release [FR; nϭ15]). Twenty-six patients underwent 4-year angiographic and IVUS follow-up and had matched assessments at all time points (index and 4-, 12-, 24-, and 48-month follow-up). One death occurred during the study period in a patient with a patent SES. There were no target-vessel revascularizations or thromboses between 2-and 4-year follow-up examinations. There was no stent thrombosis, target-lesion revascularization, death, or myocardial infarction in the SR group up to 4 years. Cumulative event-free survival rate was 87% for the total population (80% in the FR group and 93% in the SR group). In-stent late loss was slightly greater in the FR group (0.41Ϯ0.49 mm) than the SR group (0.09Ϯ0.23) after 4 years. One patient in the FR group had a 52% in-stent restenosis lesion. Percent neointimal hyperplasia volume, as detected by IVUS, remained minimal after 4 years (FRϭ9.1% and SRϭ5.7%). Conclusions-This study confirms the longevity of the optimal outcomes observed in patients treated with sirolimuseluting Bx Velocity stents 4 years after implantation. In-stent lumen dimensions remained essentially unchanged at 4-year follow-up, particularly in the population treated with the currently available SES (SR formulation). Key Words: angiography Ⅲ restenosis Ⅲ stents D rug-eluting stent (DES) implantation is rapidly becoming the prime revascularization strategy for obstructive coronary artery disease because of reduced incidence of in-stent restenosis. 1-3 Despite much enthusiasm, only a few DES devices have proven clinical effectiveness, and longterm data are lacking.Most bioactive agents of DESs alter cell cycle division and have unpredictable long-term effects in the vessel wall. 4 These cellular effects, which may resemble the mechanism of action of radiation therapy, have raised concerns about the safety of the DES beyond the initial years after implantation. In addition, nonbiodegradable polymer coatings, as well as residual medication in some devices, remain on the stent surface in close contact with arterial wall structures and represent a potential source for late inflammation, restenosis, or other side effects. The present study provides a unique opportunity to evaluate clinical, angiographic, and intravascular ultrasound (IVUS) outcomes of patients treated with sirolimus-eluting stents (SESs) 4 years after implantation. MethodsThe study sample and study protocol have been described previously. 1 In brief, 30 consecutive patients were implanted with a single sirolimus-eluting Bx Velocity stent fro...

Controlled-release local delivery of a cell-cycle inhibitor from a nonerodable polymer-coated stent reduced neointimal formation in rabbit iliac arteries in a dose-dependent manner and represents a promising strategy for preventing restenosis.

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