Procedural Success and 30-Day Outcomes between CYPHER™ and TAXUS® Stent Implantation for the Treatment of Bifurcation Lesions —

CYPHER™ (sirolimus-eluting stent, Cordis, Johnson and Johnson, Miami, Florida) and TAXUS® (polymer-based paclitaxel-eluting stent, Boston Scientific Corporation, Natick, Massachusetts) stents are the two drug-eluting stents (DES) currently approved by the Food and Drug Administration (FDA) for clinical use. Both DES have been proven effective in reducing the risks of restenosis and repeat revascularization in simple coronary lesions.^1,2 There are fundamental differences between the CYPHER and TAXUS stents, including the drug coatings, polymers and stent platforms. The stent platform for CYPHER is the BX Velocity™ coronary stent (Cordis Corp.) which uses a closed-cell design, while that for the TAXUS is the Express2™ stent uses an open-cell design. There has been concern that the different stent designs may have an impact on the treatment of bifurcation lesions. In this registry study, we sought to investigate the procedural success and 30-day outcomes of the patients who were treated with either the CYPHER or TAXUS stent for de novo bifurcation lesions. Methods Patient population. A registry on DES was started in our institution in June 2002 when the CYPHER stent was approved for clinical use. Patients who underwent 1 or more DES implantations for the treatment of de novo bifurcation lesions from June 2002 to May 2004 were recruited for analysis. As of the registry’s definition of bifurcation, the side branch had to be > 2 mm in diameter by visual estimation. The bifurcation lesions were classified according to the Institut Cardiovasculaire Paris Sud (ICPS) classification.³ The Type 1 “true” bifurcation lesion involves the main vessel proximal and distal to the bifurcation and the ostium of the side branch; the Type 2 lesion involves the main branch at the bifurcation site, but not the ostium of the side branch; the Type 3 lesion is located proximal to the bifurcation; and the Type 4 lesion is distal to the bifurcation in both branches, in the main branch only (Type 4a), or in the side branch only (Type 4b). Procedural details. All procedures were performed according to standard techniques and the interventional strategy, including the approach to the side branch and the choice of DES, which was left to the discretion of the individual operator. All patients were on lifelong aspirin and received a loading dose of clopidogrel (300 mg), which was maintained for > 3 months (75 mg/day). During the study period, CYPHER stents were available in diameters from 2.25–3.00 mm, and lengths from 8–33 mm, while the TAXUS stents were available in diameters from 2.25–3.5 mm, and lengths from 8–32 mm. The diagnosis of post-procedural myocardial infarction (MI) required an elevation of creatine kinase (CK) levels to twice the upper limit of normal, together with an increase in the CK-MB fraction. Patients who already had elevated CK levels above the baseline before the procedure were excluded for the analysis of postprocedural MI. Clinical follow-up was performed at 1 month by clinic review and/or telephone interview by dedicated research nurses. Procedural success was defined as 20% residual stenosis by visual assessment and TIMI 2–3 flow. It was considered occluded when the flow was TIMI 0–1. Adverse events, including death, MI, stroke and repeat target vessel revascularization (TVR) were recorded. The procedural success and adverse event rates at 30 days for the patients who were treated with CYPHER and TAXUS stents were compared. Statistical analysis. All statistical analyses were carried out using SPSS (version 11.5).Associations between categorical variables and stents were assessed using Chi-square or Fisher’s exact tests. A normality test was carried out for the continuous variables. Two sample t-tests were performed if the normality and equality of variances assumptions were satisfied; otherwise, the Mann Whitney U-test was used. Logistic regression analysis predicting adverse events at 30 days and procedural success between the 2 stents, adjusting for relevant covariates, were performed. Results Patient and lesion characteristics. A total of 83 patients (CYPHER = 25; TAXUS = 58) were included in this study. The mean (SD) and median (range) age of the patients was 58.1 (10.0) and 58 (33–83), respectively. Most of them were male (81.9%). Baseline patient characteristics by stent type are listed in Table 1. There was a trend toward a higher incidence of previous percutaneous coronary intervention in the CYPHER group (24% versus 7%) and diabetic patients in the TAXUS group (40% versus 24%). As is the case with the country’s ethnic group profile, the Chinese (68.7%) constituted the majority in our study population. A total of 85 bifurcation lesions (CYPHER = 25; TAXUS = 60) were studied. The lesion characteristics were not significantly different between CYPHER and TAXUS groups (Table 2). Procedural characteristics. Procedural details and quantitative coronary angiographic data on the main vessel are shown in Tables 3 and 4, respectively. Side branch intervention was performed in approximately half of the patients in both groups, and the majority underwent balloon angioplasty only (CYPHER = 92%, TAXUS = 66%). Bifurcation stenting was performed in a minority of the cases, and was more frequent in the TAXUS group. Among the patients who underwent bifurcation stenting, with the exception of 1 case where crush-stenting (TAXUS) was employed, T-stenting was the adopted strategy. At the conclusion of the procedure, the side branch was pinched in 68% and 48%, and occluded in 4% and 5% of the lesions in the CYPHER and TAXUS groups, respectively (p = 0.244). The procedural time was significantly longer in the TAXUS group, probably due to the higher incidence of bifurcation stenting in the TAXUS group. Two patients each in the CYPHER (8%) and TAXUS (3%) groups had a CK elevation above normal after the procedure (p = 0.577). But in all cases, peak CK levels were slightly less than 2 times normal, and therefore not classified as an MI. Two (1 in each group) of these 4 patients who had CK elevation after the procedure had side branch occlusion after the stent had been implanted in the main vessel. Procedural success was achieved in 96% (95% CI 80–100) for the CYPHER group, and 93% (95% CI 84–98) for the TAXUS group. After adjusting for the patient’s age, smoking status, history of diabetes mellitus and stroke, baseline hemoglobin, platelet and creatinine, side branch protection, side branch intervention and final kissing balloon angioplasty, there was no significant difference in procedural success between the CYPHER and TAXUS groups (p = 0.999). Clinical outcomes. At 30-day follow up, 2 patients in the TAXUS and none in the CYPHER group had SAT that led to MI. Urgent PCI was attempted in these 2 patients but failed in 1 of them. A total of 6 adverse events (1 stroke, 2 MIs and 3 TVRs) from 4 patients (2 patients with 2 adverse events) in the TAXUS group, and 1 adverse event (TVR) in the CYPHER group were reported. The adverse event rate was slightly, but not significantly, higher in the TAXUS group (7% versus 4%; p = 1.000). No significant difference was found in the adverse event rate at 30 days between the CYPHER and TAXUS groups (p = 0.926) after adjusting for age, gender, history of hypertension, diabetes mellitus, hyperlipidemia and stroke, previous MI, baseline hemoglobin, platelet and creatinine levels. Subacute stent thrombosis. There were 2 cases of SAT in the present study, both in the TAXUS group. The first case of SAT occurred in a 54-year-old male who underwent TAXUS stent implantation (2.75 x 16 mm) in the proximal left anterior descending artery (LAD) for post-MI angina. The diagonal branch was not treated. The patient developed no-reflow phenomenon and hypotension after stent implantation, requiring intra-aortic balloon pump support. The SAT occurred 5 days after the stenting procedure while the patient was still in the hospital and on dual antiplatelet therapy. Intravascular ultrasound showed residual stenosis at the distal stent edge as well as incomplete stent apposition. Direct stenting using a bare metal stent (2.75 x 16 mm) overlapping with the original TAXUS stent was performed after thrombus aspiration using an export aspiration catheter. The stented segment was postdilated with a noncompliant balloon (3.0 x 15 mm). The second case of SAT occurred in a 72-year-old female patient who underwent TAXUS stent implantation (2.25 x 16 mm, 2.25 x 16 mm) in the proximal left circumflex artery (LCx) for stable angina. The obtuse marginal branch was treated with balloon angioplasty. Bolus and infusion of eptifibatide was administered prior to the procedure. The LCx was severely calcified, and the 2 TAXUS stents could only be positioned and deployed using the “buddy wire” technique after vigorous balloon predilatation. The final angiographic result was good, however, the patient developed SAT 2 days after the procedure while the patient was still in the hospital and on dual antiplatelet therapy. The patient was sent for emergency coronary intervention. However, the attempt to cross the occluded lesion was unsuccessful despite using multiple guidewires. At 30-day follow up, both patients were stable and angina-free. Discussion The major findings of this study include the following: (1) The procedural success rate and 30-day adverse event rate were similar in patients treated with either CYPHER or TAXUS stents for de novo bifurcation lesions; (2) Despite a more conservative strategy on side branch management, 30-day adverse event rates remained low for our study population. There has been concern that the differences in design between the CYPHER and TAXUS stents may translate into different outcomes following stent implantation in bifurcation lesions. Experimental data have suggested that closed-cell designs provide a more even distribution of the drug into the vessel wall and fewer instances of plaque prolapse. On the other hand, the open-cell design has better side branch access and stent conformability, features which may be important in bifurcation lesions. At present, there are no data comparing the outcomes of patients treated with CYPHER versus TAXUS stents for bifurcation lesions. In the present study, the risks of side branch pinching and occlusion after stent implantation in the main vessel were similar in both the CYPHER and TAXUS groups. Although the patients who were treated with CYPHER stents had a slightly higher incidence of cardiac enzyme elevation after the procedure, adverse events at 30 days were not significantly different between the 2 groups. These suggest that the stent design may not have a significant impact on bifurcation lesions in the DES era. Given the frequent angiographic finding of side branch pinching after stent implantation in the main vessel, various bifurcation stenting techniques have been advocated. However, none of these approaches has been proven superior to the conservative approach of stenting in the main vessel with or without angioplasty in the side branch. In a series of 131 bifurcation lesions, the 1-year adverse event rate was 27% and 48% in patients who underwent balloon angioplasty to the side branch, and bifurcation stenting, respectively.⁴ Similarly, in another series of 92 patients, the in-hospital complication rate was 0% and 13% in those who underwent balloon angioplasty to the side branch, and bifurcation stenting, respectively.⁵ Moreover, with the use of DES, there has been concern that the higher concentration of drugs in the overlapping stent segment may induce endothelial dysfunction and thus increase the risk of stent thrombosis. Besides, in a recent series from Colombo et al, bifurcation stenting with the CYPHER stent was associated with a nonsignificantly higher restenosis rate in the side branch compared with stent implantation in the main vessel and angioplasty in the side branch.⁶ Our study further suggests that, at least in the short term, a conservative approach toward side branch management is equally safe compared with bifurcation stenting, and offers a potential cost-savings benefit. The occurrence of SAT in the TAXUS, but not in the CYPHER, group in the present study raised a concern. This finding was in concordance with the REALITY trial and a recent report from Italy.⁷ In a consecutive cohort of more than 2,000 patients in routine clinical practice, Iakovou et al. reported that the incidence of stent thrombosis was significantly higher in the TAXUS group than the CYPHER group (1.7% versus 0.8%). Moreover, stent implantation in bifurcation lesions was an independent predictor of stent thrombosis.⁷Study limitations. The choice of DES and the strategies for side branch intervention was nonrandomized. In addition, the sample size was relatively small, and any difference between the techniques was not statistically significant. We did not take the percent residual stenosis on the side branch into consideration in the definition of procedural success. It is a common experience that as long as a final TIMI 2–3 flow is achieved, patients seldom experience recurrent angina due to the residual side branch stenosis. We acknowledge that this hypothesis needs further evaluation. Conclusion Our results suggest that the procedural success and 30-day outcomes were similar in patients who had received either the CYPHER or TAXUS stent for de novo bifurcation lesions. The occurrence of SAT in the TAXUS, but not in the CYPHER, group warrants further evaluation. Randomized studies with longer follow up from a larger population are needed to fully determine the impact of different stent designs in bifurcation lesions in the DES era.

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