Kengo Tanabe

Unrestricted Utilization of Sirolimus-Eluting Stents Compared With Conventional Bare Stent Implantation in the “Real World” The Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) Registry

Background—The effectiveness of sirolimus-eluting stents in unselected patients treated in the daily practice is currently unknown. Methods and Results—Sirolimus-eluting stent implantation has been used as the default strategy for all percutaneous procedures in our hospital as part of the R apamycin-E luting S tent E valuated A t R otterdam C ardiology H ospital (RESEARCH) registry. Consecutive patients with de novo lesions (n=508) treated exclusively with sirolimus-eluting stents (SES group) were compared with 450 patients who received bare stents in the period just before (pre-SES group). Patients in the SES group more frequently had multivessel disease, more type C lesions, received more stents, and had more bifurcation stenting. At 1 year, the cumulative rate of major adverse cardiac events (death, myocardial infarction, or target vessel revascularization) was 9.7% in the SES group and 14.8% in the pre-SES group (hazard ratio [HR], 0.62 [95% CI, 0.44 to 0.89]; P =0.008). The 1-year risk of clinically driven target vessel revascularization in the SES group and in the pre-SES group was 3.7% versus 10.9%, respectively (HR, 0.35 [95% CI, 0.21 to 0.57]; P <0.001). Conclusions—Unrestricted utilization of sirolimus-eluting stents in the “real world” is safe and effective in reducing both repeat revascularization and major adverse cardiac events at 1 year compared with bare stent implantation.

Intravascular Ultrasound Findings in the Multicenter, Randomized, Double-Blind RAVEL (RAndomized study with the sirolimus-eluting VElocity balloon-expandable stent in the treatment of patients with de novo native coronary artery Lesions) Trial

Background—The goal of this intravascular ultrasound investigation was to provide a more detailed morphological analysis of the local biological effects of the implantation of a sirolimus-eluting stent compared with an uncoated stent. Methods and Results—In the RAVEL trial, 238 patients with single de novo lesions were randomized to receive either an 18-mm sirolimus-eluting stent (Bx VELOCITY stent, Cordis) or an uncoated stent (Bx VELOCITY stent). In a subset of 95 patients (sirolimus-eluting stent=48, uncoated stent=47), motorized intravascular ultrasound pullback (0.5 mm/s) was performed at a 6-month follow-up. Stent volumes, total vessel volumes, and plaque-behind-stent volumes were comparable. However, the difference in neointimal hyperplasia (2±5 versus 37±28 mm3) and percent of volume obstruction (1±3% versus 29±20%) at 6 months between the 2 groups was highly significant (P <0.001), emphasizing the nearly complete abolition of the proliferative process inside the drug-eluting stent. Analysis of the proximal and distal edge volumes showed no significant difference between the 2 groups in external elastic membrane or lumen and plaque volume at the proximal and distal edges. There was also no evidence of intrastent thrombosis or persisting dissection at the stent edges. Although there was a higher incidence of incomplete stent apposition in the sirolimus group compared with the uncoated stent group (P <0.05), it was not associated with any adverse clinical events at 1 year. Conclusions—Sirolimus-eluting stents are effective in preventing neointimal hyperplasia without creating edge effect and without affecting the plaque burden behind the struts.

TAXUS III Trial In-Stent Restenosis Treated With Stent-Based Delivery of Paclitaxel Incorporated in a Slow-Release Polymer Formulation

Background—The first clinical study of paclitaxel-eluting stent for de novo lesions showed promising results. We performed the TAXUS III trial to evaluate the feasibility and safety of paclitaxel-eluting stent for the treatment of in-stent restenosis (ISR). Methods and Results—The TAXUS III trial was a single-arm, 2-center study that enrolled 28 patients with ISR meeting the criteria of lesion length ≤30 mm, 50% to 99% diameter stenosis, and vessel diameter 3.0 to 3.5 mm. They were treated with one or more TAXUS NIRx paclitaxel-eluting stents. Twenty-five patients completed the angiographic follow-up at 6 months, and 17 of these underwent intravascular ultrasound (IVUS) examination. No subacute stent thrombosis occurred up to 12 months, but there was one late chronic total occlusion, and additional 3 patients showed angiographic restenosis. The mean late loss was 0.54 mm, with neointimal hyperplasia volume of 20.3 mm3. The major adverse cardiac event rate was 29% (8 patients; 1 non-Q-wave myocardial infarction, 1 coronary artery bypass grafting, and 6 target lesion revascularization [TLR]). Of the patients with TLR, 1 had restenosis in a bare stent implanted for edge dissection and 2 had restenosis in a gap between 2 paclitaxel-eluting stents. Two patients without angiographic restenosis underwent TLR as a result of the IVUS assessment at follow-up (1 incomplete apposition and 1 insufficient expansion of the stent). Conclusions—Paclitaxel-eluting stent implantation is considered safe and potentially efficacious in the treatment of ISR. IVUS guidance to ensure good stent deployment with complete coverage of target lesion may reduce reintervention.

Coronary Restenosis After Sirolimus-Eluting Stent Implantation Morphological Description and Mechanistic Analysis From a Consecutive Series of Cases

Background We describe the clinical and morphological patterns of restenosis after sirolimus‐eluting stent (SES) implantation. Methods and Results From 121 patients with coronary angiography obtained >30 days after SES implantation, restenosis (diameter stenosis >50%) was identified in 19 patients and 20 lesions (located at the proximal 5‐mm segment in 30% or within the stent in 70%). Residual dissection after the procedure or balloon trauma outside the stent was identified in 83% of the proximal edge lesions. Lesions within the stent were focal, and stent discontinuity was identified in some lesions evaluated by intravascular ultrasound. Conclusions Sirolimus‐eluting stent edge restenosis is frequently associated with local trauma outside the stent. In‐stent restenosis occurs as a localized lesion, commonly associated with a discontinuity in stent coverage. Local conditions instead of intrinsic drug‐resistance to sirolimus are likely to play a major role in post‐SES restenosis. (Circulation. 2003; 108:257‐260.)

Sirolimus-eluting stent for treatment of complex in-stent restenosis: the first clinical experience.

OBJECTIVES In this study, we assess the value of sirolimus eluting stent (SES) implantation in patients with complex in-stent restenosis (ISR). BACKGROUND The treatment of ISR remains a therapeutic challenge, since many pharmacological and mechanical approaches have shown disappointing results. The SESs have been reported to be effective in de-novo coronary lesions. METHODS Sixteen patients with severe, recurrent ISR in a native coronary artery (average lesion length 18.4 mm) and objective evidence of ischemia were included. They received one or more 18 mm Bx VELOCITY SESs (Cordis Waterloo, Belgium). Quantitative angiographic and three-dimensional intravascular ultrasound (IVUS) follow-up was performed at four months, and clinical follow-up at nine months. RESULTS The SES implantation (n = 26) was successful in all 16 patients. Four patients had recurrent restenosis following brachytherapy, and three patients had totally occluded vessels preprocedure. At four months follow-up, one patient had died and three patients had angiographic evidence of restenosis (one in-stent and two in-lesion). In-stent late lumen loss averaged 0.21 mm and the volume obstruction of the stent by IVUS was 1.1%. At nine months clinical follow-up, three patients had experienced four major adverse cardiac events (two deaths and one acute myocardial infarction necessitating repeat target vessel angioplasty). CONCLUSIONS The SES implantation in patients with severe ISR lesions effectively prevents neointima formation and recurrent restenosis at four months angiographic follow-up.

Angiographic Findings of the Multicenter Randomized Study With the Sirolimus-Eluting Bx Velocity Balloon-Expandable Stent (RAVEL) Sirolimus-Eluting Stents Inhibit Restenosis Irrespective of the Vessel Size

Background—Restenosis remains the major limitation of coronary catheter-based intervention. In small vessels, the amount of neointimal tissue is disproportionately greater than the vessel caliber, resulting in higher restenosis rates. In the Randomized Study With the Sirolimus-Eluting Bx Velocity Balloon-Expandable Stent (RAVEL) trial, ≈40% of the vessels were small (<2.5 mm). The present study evaluates the relationship between angiographic outcome and vessel diameter for sirolimus-eluting stents. Methods and Results—Patients were randomized to receive either an 18-mm bare metal Bx VELOCITY (BS group, n=118), or a sirolimus-eluting Bx VELOCITY stent (SES group, n=120). Subgroups were stratified into terciles according to their reference diameter (RD; stratum I, RD <2.36 mm; stratum II, RD 2.36 mm to 2.84 mm; stratum III, RD >2.84 mm). At 6-month follow-up, the restenosis rate in the SES group was 0% in all strata (versus 35%, 26%, and 20%, respectively, in the BS group). In-stent late loss was 0.01±0.25 versus 0.80±0.43 mm in stratum I, 0.01±0.38 versus 0.88±0.57 mm in stratum II, and −0.06±0.35 versus 0.74±0.57 mm in stratum III (SES versus BS). In SES, the minimal lumen diameter (MLD) remained unchanged (&Dgr; −0.72 to 0.72 mm) in 97% of the lesions and increased (=late gain, &Dgr;MLD <−0.72 mm) in 3% of the lesions. Multivariate predictors for late loss were treatment allocation (P <0.001) and postprocedural MLD (P = 0.008). Conclusions—Sirolimus-eluting stents prevent neointimal proliferation and late lumen loss irrespective of the vessel diameter. The classic inverse relationship between vessel diameter and restenosis rate was seen in the bare stent group but not in the sirolimus-eluting stent group.

Persistent inhibition of neointimal hyperplasia after sirolimus-eluting stent implantation: long-term (up to 2 years) clinical, angiographic, and intravascular ultrasound follow-up

Background—Early results of sirolimus-eluting stent implantation showed a nearly complete abolition of neointimal hyperplasia. The question remains, however, whether the early promising results will still be evident at long-term follow-up. The objective of our study was to evaluate the efficiency of sirolimus-eluting stent implantation for up to 2 years of follow-up. Methods and Results—Fifteen patients with de novo coronary artery disease were treated with 18-mm sirolimus-eluting Bx-Velocity stents (Cordis) loaded with 140 &mgr;g sirolimus/cm2 metal surface area in a slow release formulation. Quantitative angiography (QCA) and intravascular ultrasound (IVUS) were performed according to standard protocol. Sirolimus-eluting stent implantation was successful in all 15 patients. During the in-hospital course, 1 patient died of cerebral hemorrhage after periprocedural administration of abciximab, and 1 patient underwent repeat stenting after 2 hours because of edge dissection that led to acute occlusion. Through 6 months and up to 2 years of follow-up, no additional events occurred. QCA analysis revealed no significant change in stent minimal lumen diameter or percent diameter stenosis, and 3-dimensional IVUS showed no significant deterioration in lumen volume. In 2 patients, additional stenting was performed because of significant lesion progression remote from the sirolimus-eluting stent. Conclusion—Sirolimus-eluting stents showed persistent inhibition of neointimal hyperplasia for up to 2 years of follow-up.

Incomplete Stent Apposition After Implantation of Paclitaxel-Eluting Stents or Bare Metal Stents Insights From the Randomized TAXUS II Trial

Background—The clinical impact of late incomplete stent apposition (ISA) for drug-eluting stents is unknown. We sought to prospectively investigate the incidence and extent of ISA after the procedure and at 6-month follow-up of paclitaxel-eluting stents in comparison with bare metal stents (BMS) and survey the clinical significance of ISA over a period of 12 months. Methods and Results—TAXUS II was a randomized, double-blind study with 536 patients in 2 consecutive cohorts comparing slow-release (SR; 131 patients) and moderate-release (MR; 135 patients) paclitaxel-eluting stents with BMS (270 patients). This intravascular ultrasound (IVUS) substudy included patients who underwent serial IVUS examination after the procedure and at 6 months (BMS, 240 patients; SR, 113; MR, 116). The qualitative and quantitative analyses of ISA were performed by an independent, blinded core laboratory. More than half of the instances of ISA observed after the procedure resolved at 6 months in all groups. No difference in the incidence of late-acquired ISA was observed among the 3 groups (BMS, 5.4%; SR, 8.0%; MR, 9.5%; P=0.306), with a similar ISA volume (BMS, 11.4 mm3; SR, 21.7 mm3; MR, 8.5 mm3; P=0.18). Late-acquired ISA was the result of an increase of vessel area without change in plaque behind the stent. Predictive factors of late-acquired ISA were lesion length, unstable angina, and absence of diabetes. No stent thrombosis occurred in the patients diagnosed with ISA over a period of 12 months. Conclusions—The incidence and extent of late-acquired ISA are comparable in paclitaxel-eluting stents and BMS. ISA is a pure IVUS finding without clinical repercussions.

Incidence and clinical impact of coronary stent fracture after sirolimus-eluting stent implantation

Background: Stent fracture is one of the possible causes of restenosis after sirolimus‐eluting stents (SES) implantation. The aim of our study was to evaluate the prevalence and clinical impact of coronary stent fracture after SES implantation. Methods: From our prospective institutional database, 280 patients were treated solely with SES from August 2004 to June 2005. Among the 280 patients, 256 patients with a total of 307 lesions underwent follow‐up angiography on an average of 240 days after the procedure. Results: Stent fractures were observed in eight (2.6%) lesions. Of the eight lesions with stent fracture, five were located in the right coronary artery (RCA), two in the saphenous vein (SV) graft, and one in the left anterior descending coronary artery. The stent fractures were all in the locations that served as hinges during vessel movement in the cardiac contraction cycle. Seven of the eight stent fractures were adjacent to the edge of previously implanted or overlapped stent. Significant multivariate predictors of stent fracture were SV graft location (Odds ratio 35.88; 95% confidence interval 2.73–471.6, P = 0.006), implanted stent length (Odds ratio 1.04; 95% confidence interval 1.01–1.07, P = 0.02), and RCA location (Odds ratio 10.00; 95% confidence interval 1.11–89.67, P = 0.04). In‐stent binary restenosis rate was 37.5% and target lesion repeat revascularization rate was 50.0% in patients with stent fracture. Conclusions: Stent fracture was likely to be affected by mechanical stress provoked by rigid structures and hinge points. Stent fracture might be associated with the high incidence of target lesion revascularization.

Early Outcome After Sirolimus-Eluting Stent Implantation in Patients With Acute Coronary Syndromes Insights From the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) Registry

OBJECTIVES This study evaluated the early outcomes of patients with acute coronary syndromes (ACS) treated with sirolimus-eluting stents (SES). BACKGROUND The safety of SES implantation in patients with a high risk for early thrombotic complications is currently unknown. METHODS Sirolimus-eluting stents have been utilized as the device of choice for all percutaneous procedures in our institution, as part of the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry. After four months of enrollment, 198 patients with ACS had been treated exclusively with SES (64% of those treated in the period) and were compared with a control group composed of 301 consecutive patients treated with bare stents in the same time period immediately before this study. The incidence of major adverse cardiac events (MACE) during the first month was evaluated (death, nonfatal myocardial infarction [MI], or re-intervention). RESULTS Compared with control patients, patients treated with SES had more primary angioplasty (95% vs. 77%; p < 0.01), more bifurcation stenting (13% vs. 5%; p < 0.01), less previous MI (28% vs. 45%; p < 0.01), and less glycoprotein IIb/IIIa inhibitor utilization (27% vs. 42%; p < 0.01). The 30-day MACE rate was similar between both groups (SES 6.1% vs. control patients 6.6%; p = 0.8), with most complications occurring during the first week. Stent thrombosis occurred in 0.5% of SES patients and in 1.7% of control patients (p = 0.4). In multivariate analysis, SES utilization did not influence the incidence of MACE (odds ratio 1.0 [95% confidence interval: 0.4 to 2.2]; p = 0.97). CONCLUSIONS Sirolimus-eluting stent implantation for patients with ACS is safe, with early outcomes comparable with bare metal stents.