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, approximately 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 tertiles 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 (Delta -0.72 to 0.72 mm) in 97% of the lesions and increased (=late gain, DeltaMLD <-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.

Intracoronary beta-radiation to reduce restenosis after balloon angioplasty and stenting; the Beta Radiation In Europe (BRIE) study.

AIMS: The BRIE trial is a registry evaluating the safety and performance of (90)Sr delivered locally (Beta-Cath TM system of Novoste) to de-novo and restenotic lesions in patients with up to two discrete lesions in different vessels. METHODS AND RESULTS: In total, 149 patients (175 lesions) were enrolled; 62 treated with balloons and 113 with stents. The restenosis rate, the minimal luminal diameter and the late loss were determined in three regions of interest: (a) in a subsegment of 5mm containing the original minimal luminal diameter pre-intervention termed target segment; (b) the irradiated segment, 28 mm in length, and (c) the entire analysed segment, 42 mm in length, termed the vessel segment. Binary restenosis was 9.9% for the target segment, 28.9% for the irradiated segment, and 33.6% for the vessel segment. These angiographic results include 5.3% total occlusions. Excluding total occlusions binary restenosis was 4.9%, 25% and 29.9%, respectively. At 1 year the incidence of major adverse cardiac events placed in a hierarchical ranking were: death 2%, myocardial infarction 10.1%, CABG 2%, and target vessel revascularization 20.1%. The event-free survival rate was 65.8%. Non-appropriate coverage of the injured segment by the radioactive source termed geographical miss affected 67.9% of the vessels, and increased edge restenosis significantly (16.3% vs 4.3%, P=0.004). It accounted for 40% of the treatment failures. CONCLUSION: The results of this registry reflect the learning process of the practitioner. The full therapeutic potential of this new technology is reflected by the restenosis rate at the site of the target segment. It can only be unravelled once the incidence of late vessel occlusion and geographical miss has been eliminated by the prolonged use of thienopyridine, the appropriate training of the operator applying this new treatment for restenosis prevention, and the use of longer sources.

Geographical miss during catheter-based intracoronary beta-radiation: incidence and implications in the BRIE study. Beta-Radiation In Europe.

OBJECTIVES: We sought to determine the incidence and causes of geographical miss (GM) and to evaluate its impact on edge restenosis after intracoronary beta-radiation therapy. BACKGROUND: Edge restenosis is a limitation of intracoronary beta-radiation therapy. Geographical miss is the situation in which the radiation source does not fully cover the injured segment and may lead to edge restenosis. METHODS: We analyzed 175 vessels treated according to the Beta-Radiation In Europe (BRIE) study protocol. The effective irradiated segment (EIRS) and both edges were studied with quantitative coronary angiography. The edges of the EIRS that were injured constituted the GM edges. Restenosis was defined as diameter stenosis >50% at follow-up. Geographical miss was determined by simultaneous electrocardiographic-matched, side-by-side projection of the source and balloons deflated at the injury site, in identical angiographic projections surrounded by contrast. RESULTS: Geographical miss affected 41.2% of the edges and increased edge restenosis significantly compared with non-GM edges (16.3% vs. 4.3%, respectively, p = 0.004). Restenosis was increased both in the proximal (p = 0.05) and distal (p = 0.02) GM edges compared with noninjured edges. Geographical miss associated with stent injury significantly increased edge restenosis (p = 0.006), whereas GM related to balloon injury did not significantly increase edge restenosis (p = 0.35). The restenosis in the EIRS was similar between vessels with and without GM (24.3% and 21.6%, respectively, p = 0.8). CONCLUSIONS: Geographical miss is strongly associated with restenosis at the edges of the EIRS. This effect is more prominent when caused by stenting. Geographical miss does not increase restenosis in the EIRS.

Continued benefit of coronary stenting versus balloon angioplasty: five-year clinical follow-up of Benestent-I trial.

OBJECTIVES: This study sought to establish whether the early favorable results in the Benestent-I randomized trial comparing elective Palmaz-Schatz stent implantation with balloon angioplasty in 516 patients with stable angina pectoris are maintained at 5 years. BACKGROUND: The size of the required sample was based on a 40% reduction in clinical events in the stent group. Seven months and one-year follow-up in this trial showed a decreased incidence of restenosis and clinical events in patients randomized to stent implantation. METHODS: Data at five years were collected by outpatient visit, via telephone and via the referring cardiologist. Three patients in the stent group and one in the percutaneous transluminal coronary angioplasty (PTCA) group were lost to follow-up at five years. Major clinical events, anginal status and use of cardiac medication were recorded according to the intention to treat principle. RESULTS: No significant differences were found in anginal status and use of cardiac medication between the two groups. In the PTCA group, 27.3% of patients underwent target lesion revascularization (TLR) versus 17.2% of patients in the stent group (p = 0.008). No significant differences in mortality (5.9% vs. 3.1%), cerebrovascular accident (0.8% vs. 1.2%), myocardial infarction (9.4% vs. 6.3%) or coronary bypass surgery (11.7% vs. 9.8%) were found between the stent and PTCA groups, respectively. At five years, the event-free survival rate (59.8% vs. 65.6%; p = 0.20) between the stent and PTCA groups no longer achieved statistical significance. CONCLUSIONS: The original 10% absolute difference in TLR in favor of the stent group has remained unchanged at five years, emphasizing the long-term stability of the stented target site.

Endoluminal beta-radiation therapy for the prevention of coronary restenosis after balloon angioplasty. The Dose-Finding Study Group.

BACKGROUND: Beta radiation is effective in reducing vascular neointimal proliferation in animals after injury caused by balloon angioplasty. However, the lowest dose that can prevent restenosis after coronary angioplasty has yet to be determined. METHODS: After successful balloon angioplasty of a previously untreated coronary stenosis, 181 patients were randomly assigned to receive 9, 12, 15, or 18 Gy of radiation delivered by a centered yttrium-90 source. Adjunctive stenting was required in 28 percent of the patients. The primary end point was the minimal luminal diameter six months after treatment, as a function of the delivered dose of radiation. RESULTS: At the time of follow-up coronary angiography, the mean minimal luminal diameter was 1.67 mm in the 9-Gy group, 1.76 mm in the 12-Gy group, 1.83 mm in the 15-Gy group, and 1.97 mm in the 18-Gy group (P=0.06 for the comparison of 9 Gy with 18 Gy), resulting in restenosis rates of 29 percent, 21 percent, 16 percent, and 15 percent, respectively (P=0.14 for the comparison of 9 Gy with 18 Gy). At that time, 86 percent of the patients had had no serious cardiac events. In 130 patients treated with balloon angioplasty alone, restenosis rates were 28 percent, 17 percent, 16 percent, and 4 percent, respectively (P=0.02 for the comparison of 9 Gy with 18 Gy). Among these patients, there was a dose-dependent enlargement of the lumen in 28 percent, 50 percent, 45 percent, and 74 percent of patients, respectively (P<0.001 for the comparison of 9 Gy with 18 Gy). The rate of repeated revascularization was 18 percent with 9 Gy and 6 percent with 18 Gy (P=0.26). CONCLUSIONS: Intracoronary beta radiation therapy produces a significant dose-dependent decrease in the rate of restenosis after angioplasty. An 18-Gy dose not only prevents the renarrowing of the lumen typically observed after successful balloon angioplasty, but actually induces luminal enlargement.

The ESSEX (European Scimed Stent Experience) study.

The aim of the study was to assess the safety and feasibility of implantation of the Scimed Radius stent. Secondary objectives were to assess the result of stent placement by quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). The ESSEX study was a prospective, multicenter, observational study in which candidates for a single elective stent implantation, in a de novo or restenotic lesion, reference diameter 2.75-4.00 mm and target lesion < 14 mm in length, were enrolled. QCA at baseline, postprocedure, and 6-month follow-up was performed. IVUS was used to assess optimal stent implantation. One hundred and three patients were enrolled. Forty-four percent of the patients had unstable angina. Stent implantation was technically successful in all patients. Additional stents were implanted in 17 patients for procedural dissection (16) and spasm (1). Ninety-seven percent of patients were event-free at 1 month and 76% at 6-month follow-up. Angiographic restenosis rates for de novo lesions and for all patients were 19% and 21%, respectively. Clinical events occurred at 1- and 6-month follow-up in 2.9% and 24.3% of patients, respectively. No patients suffered subacute thrombosis. Retrospective analysis of peak balloon inflation pressure (< or = 12 and > 12 atm) as a determinant of clinical, QCA, and IVUS outcomes suggested no benefit or detrimental effect from optimization with high-pressure balloon inflation. Implantation of the self-expanding Radius stent is safe and efficacious. Based on registry data, clinical, angiographic, and IVUS, data comparable with modern balloon-expandable stents were obtained.

Three-dimensional intravascular ultrasonic volumetric quantification of stent recoil and neointimal formation of two new generation tubular stents.

Currently, several different designs of coronary stents are available. However, only a few of the new generation stents have been investigated in large randomized trials. Mechanical behavior of first-generation stents (Palmaz-Schatz, Gianturco-Roubin) may not be applied to the new designs. We investigated the chronic mechanical behavior (recoil) of 2 stents recently approved by the Food and Drug Administration (MULTILINK and NIR). Forty-eight patients with single-stent implantation (23 MULTILINK and 25 NIR) were assessed by means of volumetric 3-dimensional intravascular ultrasound analysis after the procedure and at 6-month follow-up. In addition, volumetric assessment of neointimal formation was performed. No significant chronic stent recoil was detected in both groups (delta MULTILINK stent volume: +5.6+/-41 mm3 [p = NS] and delta NIR stent volume + 2.1+/-26 mm3 [p = NS]). A similar degree of neointimal formation at 6 months was observed between the 2 stents (MULTILINK 46+/-31.9 mm3 vs NIR 39.9+/-27.6 mm3, p = NS). In conclusion, these 2 second-generation tubular stents did not show chronic recoil and appeared to promote similar proliferative response after implantation in human coronary arteries.

Reference chart derived from post-stent-implantation intravascular ultrasound predictors of 6-month expected restenosis on quantitative coronary angiography.

BACKGROUND: Intravascular ultrasound (IVUS)-guided stent implantation and the availability of a reference chart to predict the expected in-stent restenosis rate based on operator-dependent IVUS parameters may interactively facilitate optimal stent placement. The use of IVUS guidance protects against undue risks of dissection or rupture. METHODS AND RESULTS: IVUS-determined post-stent-implantation predictors of 6-month in-stent restenosis on quantitative coronary angiography (QCA) were identified by logistic regression analysis. These predictors were used to construct a reference chart that predicts the expected 6-month QCA restenosis rate. IVUS and QCA data were obtained from 3 registries (MUSIC [Multicenter Ultrasound Stenting in Coronaries study], WEST-II [West European Stent Trial II], and ESSEX [European Scimed Stent EXperience]) and 2 randomized in-stent restenosis trials (ERASER [Evaluation of ReoPro And Stenting to Eliminate Restenosis] and TRAPIST [TRApidil vs placebo to Prevent In-STent intimal hyperplasia]). In-stent restenosis was defined as luminal diameter stenosis >50% by QCA. IVUS predictors were minimum and mean in-stent area, stent length, and in-stent diameter. Multiple models were constructed with multivariate logistic regression analysis. The model containing minimum in-stent area and stent length best fit the Hosmer-Lemeshow goodness-of-fit test. This model was used to construct a reference chart to calculate the expected 6-month restenosis rate. CONCLUSIONS: The expected 6-month in-stent restenosis rate after stent implantation for short lesions in relatively large vessels can be predicted by use of in-stent minimal area (which is inversely related to restenosis) and stent length (which is directly related to restenosis), both of which can be read from a simple reference chart.

Quantitative measurements of in-stent restenosis: A comparison between quantitative coronary ultrasound and quantitative coronary angiography.

While quantitative coronary angiography (QCA) remains the standard used to assess new interventional therapies, intracoronary ultrasound (ICUS) is gaining interest. The aim of the study was to determine the relationship between QCA and quantitative coronary ultrasound (QCU) measurements after stenting. Sixty-two consecutive patients with both QCA and QCU analysis after stent implantation were included in the study. The mean luminal diameter (QCU vs. QCA) were 2.74 +/- 0.46 mm and 2.41 +/- 0.49 mm (P < 0.0001), the minimal luminal diameter (MLD) 2.08 +/- 0.44 mm and 1.62 +/- 0.42 mm (P < 0. 0001), and the projected QCU MLD 1.90 +/- 0.42 mm (P < 0.0001 with respect to QCA). Percentage obstruction diameter (QCU vs. QCA) were 41.53% +/- 10.78% and 43.15% +/- 12.72% (P = NS). The stent diameter (QCU vs. QCA) were 3.54 +/- 0.65 mm and 3.80 +/- 0.37 mm (P = 0. 0004). Stent length measured by QCU were longer at 31.11 +/- 13.54 mm against 28.63 +/- 12.75 mm, P < 0.0001 with respect to QCA. In conclusion, while QCA and QCU appear to be comparable tools for measuring corrected stent diameters and stent lengths, smaller luminal diameters were found using QCA. This is of particular relevance to quantitative studies addressing absolute changes in vascular or luminal diameters. Cathet. Cardiovasc. Intervent. 48:133-142, 1999.

Periprocedural quantitative coronary angiography after Palmaz-Schatz stent implantation predicts the restenosis rate at six months: results of a meta-analysis of the BElgian NEtherlands Stent study (BENESTENT) I, BENESTENT II Pilot, BENESTENT II and MUSIC trials. Multicenter Ultrasound Stent In Coronaries.

OBJECTIVES: We aimed to identify periprocedural quantitative coronary angiographic (QCA) variables that have predictive value on long-term angiographic results and to construct multivariate models using these variables for postprocedural prognosis. BACKGROUND: Coronary stent implantation has reduced the restenosis rate significantly as compared with balloon angioplasty in short de novo lesions in coronary arteries >3 mm in size. Although the postprocedural minimal luminal diameter (MLD) is known to have significant bearing on long-term angiographic results, no practically useful model exists for prediction of angiographic outcome based on the periprocedural QCA variables. METHODS: The QCA data from patients who underwent Palmaz-Schatz stent implantation for short (<15 mm) de novo lesions in coronary arteries >3 mm and completed six months of angiographic follow-up in the four prospective clinical trials (BENESTENT I, BENESTENT II pilot, BENESTENT II and MUSIC) were pooled. Multiple models were constructed using multivariate analysis. The Hosmer-Lemeshow goodness-of-fit test was used to identify the model of best fit, and this model was used to construct a reference chart for prediction of angiographic outcome on the basis of periprocedural QCA variables. RESULTS: Univariate analysis performed using QCA variables revealed that vessel size, MLD before and after the procedure, reference area before and after the procedure, minimal luminal cross-sectional area before and after the procedure, diameter stenosis after the procedure, area of plaque after the procedure and area stenosis after the procedure were significant predictors of angiographic outcome. Using multivariate analysis, the Hosmer-Lemeshow goodness-of-fit test showed that the model containing percent diameter stenosis after the procedure and vessel size best fit the data. A reference chart was then developed to calculate the expected restenosis rate. CONCLUSIONS: Restenosis rate after stent implantation for short lesions can be predicted using the variables percent diameter stenosis after the procedure and vessel size. This meta-analysis indicates that the concept of "the bigger the better" holds true for coronary stent implantation. Applicability of the model beyond short lesions should be tested.