Abstract
Background
Dedicated IVUS analyses of the second CObalt chromium STent with Antiproliferative for Restenosis (COSTAR II) trial have not been documented. We aim to compare IVUS findings between CoStar paclitaxel-eluting stent (PES) and Taxus PES in patients enrolled in the COSTAR II trial. We also attempted to examine the possible regional impact of multiple stenting.
Methods and materials
Among the 1700 patients enrolled, 238 were assigned to an IVUS cohort including 168 patients treated by provisional multiple stenting. At 9 months, qualitative and quantitative IVUS observations including incomplete stent apposition (ISA) and neointimal proliferation (neointimal obstruction: neointimal volume/stent volume ×100) were compared between CoStar and Taxus PESs.
Results
In qualitative analysis, late-acquired ISA was observed in 1 patient treated by Taxus PES. Impaired strut continuity suggestive of stent fracture was observed in 2 out of 33 patients treated by multiple CoStar, and 4 out of 21 patients treated by multiple Taxus ( P =.14). No such findings were found in single-stented patients in either stent subset. Quantitative analysis showed greater neointimal obstruction in CoStar (19.7%±13.4%, n =52) than in Taxus (10.7%±9.9%, n =38), whereas no significant difference in neointimal obstruction was found between single and multiple stenting in either CoStar or Taxus PES.
Conclusions
The CoStar PES exhibits greater neointimal proliferation compared with Taxus PES at 9 months but with similar qualitative outcomes including late-acquired ISA. IVUS findings suggestive of stent fracture were found only in multiple-stenting cases irrespective of the stent used.
1
Introduction
Among various drug-eluting stents (DESs) introduced thus far, the CoStar paclitaxel-eluting stent (PES) (Conor Medsystems, Menlo Park, CA; acquired by Cordis, Bridgewater, NJ) provides a unique feature of laser-cut holes loaded with paclitaxel and bioresorbable polymers, providing a programmable drug-elution property . In the second CObalt chromium STent with Antiproliferative for Restenosis (COSTAR II) trial, the CoStar PES and the Taxus Express PES (Boston Scientific, Natick, MA) were compared in a randomized manner in patients with de novo coronary artery lesions . Although the primary clinical and angiographic outcomes have been published , results of dedicated IVUS analyses comparing CoStar and Taxus PESs have not been documented.
In the present study, we aimed to compare the vessel response to CoStar and Taxus PESs using qualitative and quantitative IVUS analysis in patients allocated to the IVUS subset in the COSTAR II trial. Since more than half of all patients assigned to the IVUS subset were treated by multiple stents, we also sought to evaluate the possible regional impact of multiple stenting as compared with single stenting.
2
Methods
2.1
Study protocol
The COSTAR II trial is a prospective, randomized, single-blind, multicenter, non-inferiority study enrolling 1700 patients with de novo native coronary artery lesions, comparing CoStar and Taxus PESs with a 3:2 randomization ratio . Follow-up cardiac catheterization was planned at 9 months after stent implantation in the first 250 patients enrolled with multivessel coronary artery disease and in the first 100 patients with single-vessel disease. Of these 100 single-vessel patients, the first 70 had planned protocol-specified IVUS evaluation at 9 months. Also, all of the 168 patients with provisional overlapping stents underwent repeat catheterization and IVUS at 9 months. Finally, a total of 175 patients were enrolled in this IVUS study. All patients provided written informed consent prior to the procedure using a form approved by the local ethics committee.
2.2
IVUS imaging and analysis
IVUS recording was planned for a prespecified IVUS cohort at post-procedure and 9 months after stent implantation. The IVUS procedure was performed in a standard fashion using automated motorized pullback (0.5 mm/s) with commercially available imaging systems (40-MHz IVUS catheter, Boston Scientific Corp, Natick, MA, or 20-MHz IVUS catheter, Volcano Corp, Rancho Cordova, CA).All IVUS images were analyzed by an independent core laboratory (Cardiovascular Core Analysis Laboratory, Stanford, CA) blinded to the clinical and angiographic information.
In qualitative analysis, findings including incomplete stent apposition (ISA), stent-edge dissection, and tissue prolapse were evaluated. ISA was defined as one or more stent struts separated from the vessel wall with blood speckle identifiable behind the struts. ISA was classified as persistent, resolved, and late-acquired as previously described . Strut continuity was regarded as intermittent when stent struts were found to be separated, subluxated, or intussuscepted on IVUS images .
Commercially available 3-dimensional reconstruction software (echoPlaque, Indec Systems, Santa Clara, CA) was used for quantitative analysis. Lumen and vessel contours were traced with 0.5 mm axial intervals at both stented and reference vessel segments (defined as 5 mm segment proximal or distal adjacent to the stent). In stented segments, the stent contours were additionally traced. Plaque area outside of stent struts (peri-stent plaque area) was calculated by subtracting stent area from vessel area. For volumetric analysis, volumes (lumen, stent, peri-stent plaque, vessel, and neointima) were calculated using Simpson’s rule. To adjust for different stent length, each volume was divided by stent length (volume index: VI, mm 3 /mm). Neointimal obstruction was calculated as the ratio between the neointimal volume and stent volume ×100.Cross-sectional narrowing (CSN) was defined as neointimal area divided by stent area (%). Minimum lumen area (MLA) was also obtained from the interpolated data set of in-stent lumen area. Late area loss was calculated by subtracting MLA at follow-up from that obtained at baseline.
Results of qualitative analyses and quantitative measurements were compared between CoStar and Taxus PESs, and between single and multiple stenting. In patients treated by multiple stents, neointimal obstruction of the stented segment with strut overlapping was compared with entire stents, and with adjacent 5 mm of proximal and distal single stented segments ( Fig. 1 ).
2.3
Statistical analysis
Statistical analysis was performed using StatView 5.0 software (SAS Institute Inc., Cary, NC). Qualitative data are presented as frequencies, and quantitative data are presented as mean±SD. Categorical data were compared by χ 2 test or Fisher’s exact probability test. Continuous and ordinal variables were compared by Student’s t test or by Mann–Whitney test, respectively. Statistical significance was assumed at a value of P <.05.
2
Methods
2.1
Study protocol
The COSTAR II trial is a prospective, randomized, single-blind, multicenter, non-inferiority study enrolling 1700 patients with de novo native coronary artery lesions, comparing CoStar and Taxus PESs with a 3:2 randomization ratio . Follow-up cardiac catheterization was planned at 9 months after stent implantation in the first 250 patients enrolled with multivessel coronary artery disease and in the first 100 patients with single-vessel disease. Of these 100 single-vessel patients, the first 70 had planned protocol-specified IVUS evaluation at 9 months. Also, all of the 168 patients with provisional overlapping stents underwent repeat catheterization and IVUS at 9 months. Finally, a total of 175 patients were enrolled in this IVUS study. All patients provided written informed consent prior to the procedure using a form approved by the local ethics committee.
2.2
IVUS imaging and analysis
IVUS recording was planned for a prespecified IVUS cohort at post-procedure and 9 months after stent implantation. The IVUS procedure was performed in a standard fashion using automated motorized pullback (0.5 mm/s) with commercially available imaging systems (40-MHz IVUS catheter, Boston Scientific Corp, Natick, MA, or 20-MHz IVUS catheter, Volcano Corp, Rancho Cordova, CA).All IVUS images were analyzed by an independent core laboratory (Cardiovascular Core Analysis Laboratory, Stanford, CA) blinded to the clinical and angiographic information.
In qualitative analysis, findings including incomplete stent apposition (ISA), stent-edge dissection, and tissue prolapse were evaluated. ISA was defined as one or more stent struts separated from the vessel wall with blood speckle identifiable behind the struts. ISA was classified as persistent, resolved, and late-acquired as previously described . Strut continuity was regarded as intermittent when stent struts were found to be separated, subluxated, or intussuscepted on IVUS images .
Commercially available 3-dimensional reconstruction software (echoPlaque, Indec Systems, Santa Clara, CA) was used for quantitative analysis. Lumen and vessel contours were traced with 0.5 mm axial intervals at both stented and reference vessel segments (defined as 5 mm segment proximal or distal adjacent to the stent). In stented segments, the stent contours were additionally traced. Plaque area outside of stent struts (peri-stent plaque area) was calculated by subtracting stent area from vessel area. For volumetric analysis, volumes (lumen, stent, peri-stent plaque, vessel, and neointima) were calculated using Simpson’s rule. To adjust for different stent length, each volume was divided by stent length (volume index: VI, mm 3 /mm). Neointimal obstruction was calculated as the ratio between the neointimal volume and stent volume ×100.Cross-sectional narrowing (CSN) was defined as neointimal area divided by stent area (%). Minimum lumen area (MLA) was also obtained from the interpolated data set of in-stent lumen area. Late area loss was calculated by subtracting MLA at follow-up from that obtained at baseline.
Results of qualitative analyses and quantitative measurements were compared between CoStar and Taxus PESs, and between single and multiple stenting. In patients treated by multiple stents, neointimal obstruction of the stented segment with strut overlapping was compared with entire stents, and with adjacent 5 mm of proximal and distal single stented segments ( Fig. 1 ).
2.3
Statistical analysis
Statistical analysis was performed using StatView 5.0 software (SAS Institute Inc., Cary, NC). Qualitative data are presented as frequencies, and quantitative data are presented as mean±SD. Categorical data were compared by χ 2 test or Fisher’s exact probability test. Continuous and ordinal variables were compared by Student’s t test or by Mann–Whitney test, respectively. Statistical significance was assumed at a value of P <.05.
3
Results
3.1
CoStar PES versus Taxus PES
Among the 175 patients of the IVUS enrollment, qualitative analysis at 9 months was possible in 109 patients (CoStar: 66, Taxus: 43). Reasons for analysis exclusion were: (1) no follow-up image acquisition; (2) insufficient recording including absence of the stent-edge images; and (3)absence of calibration. In addition, 13 patients with inconsistent pullback were excluded, resulting in 90 patients (CoStar: 52, Taxus: 38) with images available for volumetric analysis at 9 months ( Fig. 2 ). When comparing the patients treated by CoStar PES ( n =52) and Taxus PES ( n =38), prevalence of hyperlipidemia was higher in patients treated by CoStar PES than in patients treated by Taxus PES. However, no significant differences were found in other patient-based or lesion-related characteristics ( Table 1 ).
| CoStar PES N =52 | Taxus PES N =38 | P | |
|---|---|---|---|
| Age, years | 61.7±9.0 | 64.8±10.0 | .12 |
| Male gender, n (%) | 36 (69.2) | 27 (71.1) | .85 |
| Diabetes mellitus, n (%) | 13 (25.0) | 10 (26.3) | .89 |
| Hyperlipidemia, n (%) | 42 (80.8) | 22 (57.9) | .02 |
| Hypertension, n (%) | 37 (71.2) | 30 (78.9) | .40 |
| Smoking, n (%) | 12 (23.1) | 9 (23.7) | .82 |
| Previous myocardial infarction, n (%) | 19 (36.5) | 10 (26.3) | .31 |
| Previous PCI, n (%) | 17 (32.7) | 11 (28.9) | .70 |
| Unstable angina, n (%) | 21 (40.4) | 15 (39.5) | .93 |
| Left ventricular ejection fraction, % | 58.9±10.8 | 58.0±10.6 | .70 |
| Target vessel, n (%) | .92 | ||
| Left anterior descending artery | 19 (36.5) | 15 (39.5) | |
| Left circumflex artery | 16 (30.8) | 12 (31.6) | |
| Right coronary artery | 17 (32.7) | 11 (28.9) | |
| Reference diameter by QCA, mm | 2.8±0.4 | 2.7±0.5 | .16 |
| Lesion length by QCA, mm | 19.4±8.2 | 19.0±7.8 | .81 |
| Single stent/multiple stents | 19/33 | 17/21 | .43 |
| Number of stent implanted (per vessel) | 1.7±0.7 | 1.5±0.5 | .06 |
| Stent size, mm | 3.0±0.4 | 2.9±0.4 | .07 |
| Stent length, mm | 29.7±12.8 | 28.9±11.2 | .75 |
| Maximum inflation pressure, atm | 13.8±6.8 | 13.3±9.8 | .48 |
3.1.1
Qualitative analysis
In the serial assessment of baseline and 9-month follow-up IVUS images (CoStar35, Taxus 23), there were no differences in the incidence or prevalence of any type of ISA, stent edge dissection, or tissue prolapse between the 2 stents ( Table 2 ). There was one case that showed late-acquired ISA ( Fig. 3 A ), but the incidence was not different between the two DESs. IVUS images obtained at 9-month follow-up showed intermittent stent–strut continuity in 6 patients (2 CoStar, 4 Taxus) whose demographics are listed in Table 3 . Representative IVUS images of the intermittent stent–strut continuity (separate-type) were shown in Fig. 3 B. The incidence was 3.8% (2/52) for CoStar PES and 10.5% (4/38) for Taxus PES ( P =.23). In these 6 cases, neointimal obstruction ranged from 1.6% to 20.9%, and none showed late-acquired ISA.
