Increased late mortality after sirolimus-eluting stents versus bare-metal stents in diseased saphenous vein grafts: results from the randomized DELAYED RRISC Trial.

OBJECTIVES: We sought to provide long-term follow-up data of sirolimus-eluting stents (SES) versus bare-metal stents (BMS) in saphenous vein grafts (SVG) from the RRISC (Reduction of Restenosis In Saphenous vein grafts with Cypher) trial. BACKGROUND: We have previously shown that, in SVG, the use of SES reduces 6-month restenosis and repeated revascularization procedures versus the use of BMS. These data are consistent with trials in native coronary arteries. However, recently published long-term follow-up data of these trials have revealed an increased risk of adverse events (particularly very late stent thrombosis) after SES. METHODS: A total of 75 patients with 96 SVG lesions were randomized to SES versus BMS. All patients underwent clinical follow-up up to 3 years. Specific outcomes assessed in this secondary post-hoc analysis were all-cause mortality, myocardial infarction, and target vessel revascularization. RESULTS: Thirty-eight patients received 60 SES for 47 lesions, whereas 37 patients received 54 BMS for 49 lesions. At a median follow-up time of 32 months (interquartile range 26.5 to 36 months), 11 deaths (7 cardiac, of which 1 was caused by very late stent thrombosis and, 3 were sudden) occurred after SES (29% [95% confidence interval (CI) 17% to 45%]) versus 0 after BMS (0% [95% CI 0% to 9%]) with an absolute difference of 29% ([95% CI 14% to 45%], p < 0.001). The rates of myocardial infarction and target vessel revascularization were not different: 18% and 34% after SES, respectively, versus 5% and 38% after BMS, respectively (p = 0.15 and p = 0.74, respectively). CONCLUSIONS: In this secondary post-hoc analysis, BMS were associated with lower long-term mortality than SES for SVG disease. Also, the 6-month reduction in repeated revascularization procedures with SES was lost at longer-term follow-up. (RRISC Study: Reduction of Restenosis In Saphenous Vein Grafts With Cypher Sirolimus-Eluting Stent; http://clinicaltrials.gov/ct/show/NCT00263263?order=1; NCT00263263).     

Palmaz-Schatz stent implantation in stenosed saphenous vein grafts: clinical and angiographic follow-up.

Balloon-expandable stents may reduce the restenosis rate following coronary angioplasty. To evaluate this potential in saphenous vein grafts, 26 patients with 30 discrete stenoses underwent conventional balloon dilation and successful Palmaz-Schatz stent implantation as part of a multicenter trial. All patients had resolution of their angina following the procedure. In a mean 5-month follow-up period, 14 patients (54%, 16 lesions) had repeat arteriography; two patients (14%) developed recurrent ischemia ascribed to their venous grafts from in-stent restenosis (2 of 16 lesions, 13%). Two asymptomatic patients (8%) died: one from cardiac arrest (stent patent) and one from stroke (no autopsy). The clinical recurrence rate (cardiac death, myocardial infarction, bypass surgery, repeat angioplasty, or symptom recurrence) was 15%. These preliminary results show trends toward an improved primary success rate with combined vein graft angioplasty/stenting and a lower restenosis rate in stented saphenous vein grafts, but continuing follow-up will be needed to verify these observations.     

Intravascular ultrasound comparison of sirolimus-eluting stent versus bare metal stent implantation in diseased saphenous vein grafts (from the RRISC [Reduction of Restenosis In Saphenous Vein Grafts With Cypher Sirolimus-Eluting Stent] trial)

The randomized Reduction of Restenosis In Saphenous Vein Grafts with Cypher Sirolimus-Eluting Stent trial compared angiographic outcomes of sirolimus-eluting stents (SESs) versus bare metal stents (BMSs) in saphenous vein grafts (SVG). Using intravascular ultrasound (IVUS) performed during 6-month follow-up angiography, we compared the vascular effects of the 2 types of stent on SVGs. Of 75 patients (96 lesions) included, 59 patients underwent IVUS in 61 SVGs; 29 patients received 40 SESs for 34 lesions, and 30 patients received 42 BMSs for 39 lesions. IVUS parameters (diameters, areas, and volumes) were compared in the 2 groups. A specific analysis was performed for overlapping SESs. Median neointimal volume was 1.3 mm(3) (interquartile range 0 to 13.1) in SESs versus 24.5 (7.8 to 39.5) in BMSs (p <0.001). Minimal incomplete stent apposition was detected at only 3 stent edges (2 BMSs, 1 SES) next to ectatic regions of the SVG. Compared with single SESs, overlapping SESs showed significant increases in neointimal reaction, with a neointimal volume of 0.6 mm(3)/mm of stent (0.1 to 1.8) versus 0 (0 to 0.4) in single SESs (p = 0.03), and this phenomenon was mainly localized in overlapping SES segments, where neointimal volume per millimeter of stent was 1.1 mm(3)/mm (0.6 to 4.4) versus 0 (0 to 1.3) in nonoverlapping segments (p = 0.05). In conclusion, SESs effectively inhibit neointimal hyperplasia volume compared with BMSs in diseased vein grafts, without evidence of increased incomplete apposition risk. The neointimal response to overlapping SES layers seems higher than to a single SES layer.     

Reproducibility of the intravascular ultrasound assessment of stent implantation in saphenous vein grafts

IVUS measurements of stent and reference lumen dimensions and cross-sectional areas are highly reproducible. Furthermore, paramedical personnel can be trained to perform these measurements accurately. Thus, IVUS measurements may become the gold standard for the acute, chronic, and serial assessment of stent implantation procedures.     

Angiographic and volumetric intravascular ultrasound comparison between direct sirolimus-eluting stent implantation versus predilation

Conventional sirolimus-eluting stent (SES) implantation typically follows balloon predilation. The impact of direct SES implantation on in-stent neointimal hyperplasia and the adjacent reference segments has not been evaluated. The aim of this study was to analyze direct and conventional SES implantation techniques by angiography and serial intravascular ultrasound. Fifty-three patients with single de novo coronary lesions underwent successful conventional (n = 26) and direct (n = 27) SES implantation. At 6-month follow-up, similar in-stent late luminal loss and decreased neointimal hyperplasia volume were seen in the 2 groups, preserving the luminal dimensions at the edges of the stents.     

Elective sirolimus-eluting stent implantation for left main coronary artery disease: six-month angiographic follow-up and 1-year clinical outcome.

The effectiveness of sirolimus-eluting stent (SES) implantation in patients treated electively for left main (LM) stenoses has not been yet ascertained. The present study reports on the clinical and angiographic outcome of 16 consecutive patients treated electively for de novo stenoses in the LM. The impact of SES implantation on major adverse cardiac events was evaluated. Mean age was 65 +/- 11 years. Unprotected LM was present in nine (56%), and eight patients (50%) received stents extending into both the left anterior descending and circumflex arteries for stenoses of the distal left main bifurcation. In-house mortality and reintervention rate was zero. One patient developed a non-Q-wave myocardial infarction related to the index procedure. At 1-year clinical follow-up, there were no deaths or further myocardial infarctions; one (6%) patient required target lesion revascularization. A total of 12 patients (75%) underwent 6-month angiographic follow-up with a late lumen loss of 0.04 +/- 0.65 mm and one focal restenosis (8% of patients). Elective SES implantation for LM disease was associated with zero mortality and a very low incidence of additional major adverse events at 1 year.     

Intravascular ultrasound predictors of angiographic restenosis after sirolimus-eluting stent implantation.

AIMS: In many countries, drug-eluting stent implantation is the dominant interventional strategy. We evaluated the clinical, angiographic, procedural, and intravascular ultrasound (IVUS) predictors of angiographic restenosis after sirolimus-eluting stent (SES) implantation. METHODS AND RESULTS: SES implantation was successfully performed in 550 patients with 670 native coronary lesions. Six-month follow-up angiography was performed in 449 patients (81.6%) with 543 lesions (81.1%). Clinical, angiographic, procedural, and IVUS predictors of restenosis were determined. Using multivariable logistic regression analysis, the only independent predictors of angiographic restenosis were post-procedural final minimum stent area by IVUS [odds ratio (OR)=0.586, 95% confidence interval (CI) 0.387-0.888, P=0.012] and IVUS-measured stent length (OR=1.029, 95% CI 1.002-1.056, P=0.035). Final minimum stent area by IVUS and IVUS-measured stent length that best separated restenosis from non-restenosis were 5.5 mm2 and 40 mm, respectively. Lesions with final minimum stent area<5.5 mm2 and stent length>40 mm had the highest rate of angiographic restenosis [17.7% (11/62)], P<0.001 compared with other groups. CONCLUSION: Independent predictors of angiographic restenosis after SES implantation were post-procedural final minimum stent area by IVUS and IVUS-measured stent length. The angiographic restenosis rate was highest in lesions with stent area<5.5 mm2 and stent length>40 mm.     

Endoluminal stenting of narrowed saphenous vein grafts: long-term clinical and angiographic follow-up

From April 1986 through April 1993, 58 intracoronary stents (41 Wall and 17 Wiktor stents) were implanted for the treatment of saphenous vein graft stenosis in 40 symptomatic patients. The indication was a primary stenosis in 44 and restenosis in 14 procedures. In-hospital complications were subacute stent thrombosis (2%), myocardial infarction (2%), and emergency coronary artery bypass grafting (CABG) (2%). Complications during a mean follow-up period of 42±27 months were restenosis (35% by patient, 33% by lesion), myocardial infarction (12%), late bypass grafting (12%), and death (7%). On quantitative coronary angiographic analysis, the mean minimal luminal diameter (and its confidence interval) increased from 1.3 mm (1.1–1.5 mm, preprocedure) to 2.9 mm (2.7–3.1 mm, postprocedure) and 2.2 mm (2.0–2.5 mm, 6 months follow-up, 95% angiographic follow-up). Progression of the underlying coronary artery disease and restenosis were the main reasons for a continual decline of the proportion without cardiac event on a Kaplan-Meier estimate. Restenosis occurred in one-third of cases beyond the first 6 months of follow-up. A relative risk ratio analysis for restenosis, performed on 14 variables, disclosed an increased risk for the following variables: (1) stenting of the proximal, distal or anastomosis part of the vein graft (relative risk 2.41, confidence interval: 1.28–3.59), (2) the implantation of stents <4.5 mm (2.59, 1.18–4.00), and (3) stenting of a redo–CABG vein graft (2.37, 1.17–3.58). Saphenous vein graft stenting seems to be characterized by excellent immediate clinical and angiographic results; in particular, stent thrombosis is rare. In this study, it appears that restenosis rates are lower than after conventional balloon angioplasty, but several procedural factors are related to an increased restenosis risk. Despite a lasting success in the majority of stented lesions, the estimated proportion without cardiac event is low at 5 years follow-up. Progression of the underlying coronary artery disease, a non-procedure-related event, constitutes the major limitation of saphenous vein graft stenting. © 1994 Wiley-Liss,Inc..     

雷帕霉素洗脱支架冠状动脉造影随访结果分析

目的通过对接受雷帕霉素洗脱支架(sirolimus-eluting stent,SES)治疗的冠心病患者冠状动脉造影随访,观察其临床实际应用的效果。方法339例患者接受治疗,所有患者均接受了临床随访,165例患者于置入术后6~12个月行冠状动脉造影复查。结果冠状动脉造影随访时,支架近端边缘晚期管腔丢失显著高于支架内及支架远端边缘(0.17 mmvs0.08 mmvs0.09 mm),再狭窄率为9.7%,再血管化率4.84%,再狭窄以局限性狭窄为主。在339例患者中,有4例患者于支架置入后5天~4个月发生猝死。猝死发生率为1.18%。1例于支架置入后14天发生支架内亚急性血栓形成,发生率0.50%。晚期血栓形成1例(术后12个月),主要心血管不良事件为1.70%。结论对复杂的冠状动脉病变SES有较好的疗效,能显著降低支架后再狭窄,减少靶血管的再血管化率。     

Late incomplete stent apposition after sirolimus-eluting stent implantation: a serial intravascular ultrasound analysis.

OBJECTIVES: We sought to identify the frequency of incomplete stent apposition (ISA) in sirolimus-eluting stents (SES) and clarify its findings and clinical sequelae. BACKGROUND: Late-acquired ISA has been reported in bare-metal stents (BMS) and brachytherapy and recently in drug-eluting stents. However, the characteristics of late ISA in SES have not been clarified. METHODS: From the SIRIUS trial, a randomized, multicenter study comparing SES and BMS, serial qualitative intravascular ultrasound (IVUS; at stent implantation and eight-month follow-up) was available in 141 patients (BMS: n = 61; SES: n = 80). The IVUS images were reviewed for the presence of ISA. RESULTS: Incomplete stent apposition at follow-up was observed in 19 patients (BMS: n = 6 [9.8%]; SES: n = 13 [16.3%]; p = NS). Among these, 12 had ISA after intervention and at follow-up (persistent ISA). Late-acquired ISA was seen in the remaining seven cases, all from the SES group (BMS: n = 0; SES: n = 7 [8.7%]; p < 0.05). In late-acquired ISA, there was an increase in external elastic membrane area (after intervention: 16.2 +/- 2.7 m2; follow-up: 18.9 +/- 3.6 mm2; p < 0.05). The location of stent-vessel wall separation was primarily at the stent edges in persistent ISA cases, whereas late-acquired ISA in SES occurred mostly in the mid portion of the stent. There were no negative clinical events reported for any ISA cases at 12-month clinical follow-up. CONCLUSIONS: Late ISA was observed in 8.7% of patients after SES implantation. There were no negative clinical events associated with this IVUS finding at 12-month clinical follow-up; however, careful long-term follow-up will be necessary.     

Comparison of six-month angiographic and three-year outcomes after sirolimus-eluting stent implantation versus brachytherapy for bare metal in-stent restenosis

To evaluate long-term effectiveness of sirolimus-eluting stent (SES) implantation for diffuse bare metal in-stent restenosis (ISR), we compared 6-month angiographic and long-term (3-year) clinical outcomes of SES implantation and intracoronary brachytherapy (ICBT). SES implantation for diffuse ISR was performed in 120 consecutive patients and their results were compared with those from 240 patients treated with beta-radiation with balloons filled with rhenium-188 and mercaptoacetyltriglycine. The radiation dose was 15 or 18 Gy at a depth of 1.0 mm into the vessel wall. The primary end point was 3-year major adverse cardiac events including myocardial infarction, cardiac death, and target lesion revascularization. The 2 groups were similar in baseline clinical and angiographic characteristics. Lesion lengths were 25.1 +/- 14.2 mm in the SES group and 24.5 +/- 10.4 mm in the ICBT group (p = 0.15). In-stent acute gain was greater in the SES group than in the ICBT group (2.23 +/- 0.62 vs 1.91 +/- 0.54 mm, p <0.001). We obtained 6-month angiographic follow-up in 287 patients (79.7%). In-segment angiographic restenoses were 7.4% (7 of 94) in the SES group and 26.4% (51 of 193) in the ICBT group (p <0.05). Two myocardial infarctions (1 in each group) and 5 deaths (4 in SES group, 1 in ICBT group) occurred during 3-year follow-up. At 3 years, survival rates without target lesion revascularization (94.1 +/- 2.2% vs 84.6 +/- 2.3%, p = 0.011) and major adverse cardiac events (92.5 +/- 2.4% vs 84.2 +/- 2.4%, respectively, p = 0.03) were higher in the SES than in the ICBT group. In conclusion, compared with ICBT, SES implantation for diffuse ISR is more effective in decreasing recurrent restenosis and improving long-term outcomes.     

Impact of various intravascular ultrasound criteria for stent optimization on the six-month angiographic restenosis.

We evaluated the impact of different intravascular ultrasound (IVUS) criteria on 6-month angiographic restenosis in 511 patients with 560 lesions. Seven IVUS criteria were evaluated in this study; stent area at lesion segment 1) > or = 100% of distal reference lumen area, 2) > or = 90% of distal reference lumen area, 3) > or = 80% of average reference lumen area, 4) > or = 90% of average reference lumen area, 5) > or = 55% of average reference vessel area, 6) >/= 7 mm(2), and 7) > or = 2). Using the relative measurement (criteria 1-5), the angiographic restenosis rate was not statistically different. However, absolute measurement of stent area > or = 9 mm(2) (criteria 6 and 7) were associated with significantly lower restenosis rate (14.8% vs. 30.9%, P = 0.001, and 13.5% vs. 24.6%, P = 0.006, respectively). In conclusions, using the relative measurement of IVUS criteria, the occurrence of angiographic restenosis might not be predicted. The absolute measurement of IVUS stent area was the predictor of angiographic restenosis.     

Retrospective comparison of clinical and angiographic outcomes after sirolimus-eluting and bare-metal stent implantation in 312 consecutive, nonrandomized severely calcified lesions using a rotablator

In order to compare the long-term clinical and angiographic outcomes after sirolimus-eluting stent (SES) and bare-metal stent (BMS) placement in severely calcified lesions using a rotablator under the widespread indication of SES, a nonrandomized examination of 312 consecutive lesions after successful implantation of a BMS (99 lesions in 84 patients; from January 2003) or SES (213 in 167; from September 2004) using a rotablator was conducted. The lesion-based primary endpoints (cardiac death and nonfatal recurrent myocardial infarction) and the secondary endpoint [binary restenosis (BR) (diameter stenosis > 50%) at follow-up angiography] were retrospectively determined in August 2010. The incidence of primary endpoint in the SES group (2.3%; mean follow-up period of 1289 ± 526 days) was significantly lower than that in the BMS group (7.1%; P = 0.043; 1803 ± 887 days), although the several variables related to the endpoints were present in the SES group. Cox proportional hazard model analysis revealed that SES was not significantly related to a primary endpoint [hazard ratio of 0.42 (95% CI, 0.073-2.42; P = 0.33)]. The incidence of BR in the SES group (21.3%) was not significantly different from that in the BMS group (27.1%) (P = 0.33). Multivariate logistic regression analysis revealed that SES was not a significant predictor of BR [Odds ratio of 0.78 (95% CI, 0.41-1.51; P = 0.47)]. Thus, although the results of the present retrospective nonrandomized study demonstrate the long-term safety of SES for calcified lesions using a rotablator in daily practice, SES did not show a benefit for the angiographic outcomes compared to BMS.     

Intravascular ultrasound imaging of saphenous vein grafts in vitro: comparison with histologic and quantitative angiographic findings.

The ubiquity of coronary artery disease and the resultant widespread use of saphenous veins for coronary artery bypass surgery has stimulated considerable interest in the morphologic and pathophysiologic alterations these vessels undergo after implantation. This study was undertaken to determine the ability of intravascular ultrasound to identify and characterize abnormalities in saphenous vein grafts. Ten saphenous vein grafts excised at autopsy and nine saphenous vein segments harvested during coronary artery bypass surgery were examined with intravascular ultrasound imaging, quantitative coronary angiographic techniques and histologic analysis. Intravascular ultrasound lumen measurements were strongly correlated with quantitative coronary arteriographic measurements (r 0.91, SEE 0.5 mm). Wall thickness was significantly greater in the vein grafts after long-term implantation than in the freshly harvested veins (average thickness 1.4 +/- 0.5 vs. 0.7 +/- 0.2 mm, p less than 0.007); this finding correlated histologically with vein wall fibrosis. There was good correlation between ultrasound imaging and histologic analysis, with the ability to distinguish among normal intima, intimal hyperplasia, vein wall fibrosis and atheromatous plaque. Thus, this preliminary study demonstrates the ability of intravascular ultrasound to provide real-time cross-sectional images of saphenous veins and morphologic characterization of their walls. This modality may have important clinical applications, including the ability to detect serial changes in vein graft intimal hyperplasia and atherosclerosis.