Abstract
Background
Randomized controlled trials have demonstrated that second-generation drug-eluting stents (DESs) for the treatment of obstructive coronary artery disease are associated with comparable, if not improved, clinical outcomes as compared to those of their first-generation counterparts. The aim of this study was to compare the long-term clinical outcomes associated with first- versus second-generation DESs for the treatment of coronary bifurcation lesions.
Methods and Materials
This was a retrospective study of consecutive de novo bifurcation lesions, excluding those at the left main, treated with either second-generation DES (everolimus-eluting or resolute zotarolimus-eluting stents) between October 2006 and October 2011 (199 bifurcation lesions in 192 patients) or first-generation DES (sirolimus-eluting or paclitaxel-eluting stents) between April 2002 and December 2005 (289 bifurcation lesions in 273 patients).
Results
Second-generation DES use in this setting was associated with less major adverse cardiac events (MACE) (23.1% vs. 14.4%, p = 0.02) as well as lower target vessel revascularization (TVR) rates (15.5% vs. 8.3%, p = 0.01) at 2-year follow-up. Target lesion revascularization, both per patient (12.6% vs. 7.4%, p = 0.02) and per bifurcation (11.8% vs. 7.0%, p = 0.03), was also improved with second-generation DES over the same follow-up period. Propensity-score adjusted analysis suggested that second-generation DES was associated with a lower incidence of MACE (HR, 0.53; 95% CI, 0.33–0.85; p = 0.01) and TVR (HR, 0.44; 95% CI, 0.24–0.83; p = 0.01).
Conclusions
Our results suggest that the use of second-generation DES for the treatment of bifurcation lesions is associated with better clinical outcomes as compared to first-generation DES, largely due to a lower need for repeat revascularization.
1
Introduction
Randomized controlled trials have demonstrated that second-generation drug-eluting stents (DESs) are at least non-inferior to first-generation DESs in the treatment of non-complex coronary lesions. In the multicenter SORT OUT IV; Scandinavian Organization for Randomized Trials with Clinical Outcome IV trial, the everolimus-eluting stent (EES) was associated with similar clinical outcomes and a lower rate of definite stent thrombosis (ST) as compared to the sirolimus-eluting stent (SES) in unselected patients with coronary artery disease at 2-years . In the SPIRIT IV: Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System trial patients treated with EES rather than the paclitaxel-eluting stent (PES) had significantly lower rates of target lesion failure as well as ST at 1-year . Another second generation DES, the zotarolimus-eluting stent (ZES), has also been associated with clinical outcomes comparable to those observed with first-generation DESs . Despite these encouraging results, the performance of second-generation DESs as compared to their first-generation counterparts in the treatment of coronary bifurcations has not been fully evaluated. Bifurcation lesions represent a high-risk lesion cohort associated with worse clinical outcomes as compared to non-bifurcation lesions . Previously, we have demonstrated that PES and SES at bifurcation sites are associated with similar but relatively high target-vessel revascularization rates (TVR), approximating 20% at a median follow-up of 35 months . The present study aimed to specifically investigate whether second-generation DESs at bifurcation sites are associated with improved long-term clinical outcomes as compared to their first-generation counterparts.
2
Methods
We compared a population of 192 patients (199 bifurcations) treated with EES (Xience Prime™ and Xience V®, Abbott Vascular, Santa Clara, CA or Promus™ and Promus Element, Boston Scientific Corp., Natick, MA) and Resolute-ZES (R-ZES, Endeavor® Resolute, Medtronic, Santa Rosa, CA) implantation on a coronary bifurcation between October 2006 and October 2011 to a population of 273 patients (289 bifurcations) treated with SES (Cypher stent, Cordis Corp., a Johnson and Johnson Company, Warren, NJ) and PES (Taxus, Boston Scientific Corp., Natick, MA) between April 2002 and December 2005 at two centers (San Raffaele Hospital and EMO-GVM Centro Cuore Columbus, Milan, Italy). Patients with left main, restenotic and trifurcation lesions as well as those with bare metal stent use along with DES to treat the same bifurcation lesion were excluded from the study. All patients provided informed consent for both the procedure, data collection and subsequent analysis for research purposes. All patients were pretreated with aspirin and either ticlopidine or clopidogrel. A 300 mg or 600 mg loading dose of clopidogrel before the index procedure was administered if patients were not pretreated. Intravenous heparin was administered to maintain an activated clotting time > 250 s during the procedure. Stent selection as well as interventional approach including platelet glycoprotein IIb/IIIa receptor inhibitor and intravascular ultrasound use was left to the discretion of the operator. In general, a provisional approach was preferred, unless significant stenosis and relatively long disease were present in a side-branch supplying significant myocardial territory or if there was evidence of dissection, plaque shift or flow compromise following implantation of the main-branch (MB) stent that did not resolve with balloon dilatation in the side-branch (SB). After the procedure, all patients were prescribed life-long aspirin therapy and clopidogrel or ticlopidine for at least 6 or 12 months. Clinical follow-up was performed on all included subjects by clinic visit or by telephone interview. Clinical outcomes reported represent patient-specific data unless otherwise stated and were all censored at 2 years.
Measured endpoints were major adverse cardiac events (MACEs) defined as composite of all-cause death, myocardial infarction (MI) including peri-procedural, and TVR. Death was considered cardiac in origin unless obvious non-cardiac causes were identified. We defined post-procedural non-Q-wave MI as a creatinine kinase-myocardial band elevation of > 3 times the upper limit of normal. Creatinine kinase was routinely measured after percutaneous coronary intervention (PCI) in all patients at both centers . Non-procedural or spontaneous MI was defined as an elevation of troponin above the upper range limit in combination with at least 1 of the following: symptoms of ischemia; electrocardiographic changes indicative of new ischemia; or the development of pathological Q waves on electrocardiogram. Target lesion revascularization (TLR) was defined as repeat revascularization for the lesion in the previously treated segment or in the adjacent 5 mm. The occurrence of ST was defined on the basis of the Academic Research Consortium definition . True bifurcation was defined as those with stenoses > 50% in both the MB and SB. A one-stent strategy refers to a strategy in which a stent was implanted either in the MB or SB whereas a two-stent strategy involved stenting of both the MB and SB. Procedural success was defined as completion of the procedure with no in-lab complications, final TIMI flow 3 with residual stenosis < 20% in the stented segment.
Continuous variables are presented as means ± SD or medians (interquartile range) and categorical variables as frequencies (%). Continuous variables were compared using the Mann–Whitney U test. Categorical variables were compared with χ 2 statistic. Because of the nonrandomized nature of the study, a propensity-score adjusted analysis was performed to minimize any selection bias due to the differences in clinical characteristics between the 2 groups. Variables included in the logistic regression model to calculate the propensity-score were age, sex, diabetes, smoking, hypertension, hypercholesterolaemia, family history of coronary artery disease, acute coronary syndrome, prior MI, prior PCI, prior coronary artery bypass graft, left ventricular ejection fraction and multivessel disease. The C-statistic was 0.63, and the Hosmer–Lemeshow test p value was 0.31, confirming good discrimination and calibration of the propensity-score model. The individual propensity-score was incorporated into Cox proportional hazards regression models as a covariate as well as stent generation as the variable of interest to calculate the adjusted hazard ratio (HR). Furthermore, multivariable Cox proportional-hazards regression modeling of the entire population was also performed to determine independent predictors of MACE and TVR, using purposeful selection of covariates. Variables associated at univariate analysis with MACE (all with a p value < 0.1) and those judged to be of clinical importance from previous published literature were eligible for inclusion into the multivariable model-building process. The final multivariable model for this analysis included diabetes, sex, ejection fraction, presence of true bifurcation, use of final balloon kissing inflation, one- vs. two-stent strategy, stent length and stent type.
2
Methods
We compared a population of 192 patients (199 bifurcations) treated with EES (Xience Prime™ and Xience V®, Abbott Vascular, Santa Clara, CA or Promus™ and Promus Element, Boston Scientific Corp., Natick, MA) and Resolute-ZES (R-ZES, Endeavor® Resolute, Medtronic, Santa Rosa, CA) implantation on a coronary bifurcation between October 2006 and October 2011 to a population of 273 patients (289 bifurcations) treated with SES (Cypher stent, Cordis Corp., a Johnson and Johnson Company, Warren, NJ) and PES (Taxus, Boston Scientific Corp., Natick, MA) between April 2002 and December 2005 at two centers (San Raffaele Hospital and EMO-GVM Centro Cuore Columbus, Milan, Italy). Patients with left main, restenotic and trifurcation lesions as well as those with bare metal stent use along with DES to treat the same bifurcation lesion were excluded from the study. All patients provided informed consent for both the procedure, data collection and subsequent analysis for research purposes. All patients were pretreated with aspirin and either ticlopidine or clopidogrel. A 300 mg or 600 mg loading dose of clopidogrel before the index procedure was administered if patients were not pretreated. Intravenous heparin was administered to maintain an activated clotting time > 250 s during the procedure. Stent selection as well as interventional approach including platelet glycoprotein IIb/IIIa receptor inhibitor and intravascular ultrasound use was left to the discretion of the operator. In general, a provisional approach was preferred, unless significant stenosis and relatively long disease were present in a side-branch supplying significant myocardial territory or if there was evidence of dissection, plaque shift or flow compromise following implantation of the main-branch (MB) stent that did not resolve with balloon dilatation in the side-branch (SB). After the procedure, all patients were prescribed life-long aspirin therapy and clopidogrel or ticlopidine for at least 6 or 12 months. Clinical follow-up was performed on all included subjects by clinic visit or by telephone interview. Clinical outcomes reported represent patient-specific data unless otherwise stated and were all censored at 2 years.
Measured endpoints were major adverse cardiac events (MACEs) defined as composite of all-cause death, myocardial infarction (MI) including peri-procedural, and TVR. Death was considered cardiac in origin unless obvious non-cardiac causes were identified. We defined post-procedural non-Q-wave MI as a creatinine kinase-myocardial band elevation of > 3 times the upper limit of normal. Creatinine kinase was routinely measured after percutaneous coronary intervention (PCI) in all patients at both centers . Non-procedural or spontaneous MI was defined as an elevation of troponin above the upper range limit in combination with at least 1 of the following: symptoms of ischemia; electrocardiographic changes indicative of new ischemia; or the development of pathological Q waves on electrocardiogram. Target lesion revascularization (TLR) was defined as repeat revascularization for the lesion in the previously treated segment or in the adjacent 5 mm. The occurrence of ST was defined on the basis of the Academic Research Consortium definition . True bifurcation was defined as those with stenoses > 50% in both the MB and SB. A one-stent strategy refers to a strategy in which a stent was implanted either in the MB or SB whereas a two-stent strategy involved stenting of both the MB and SB. Procedural success was defined as completion of the procedure with no in-lab complications, final TIMI flow 3 with residual stenosis < 20% in the stented segment.
Continuous variables are presented as means ± SD or medians (interquartile range) and categorical variables as frequencies (%). Continuous variables were compared using the Mann–Whitney U test. Categorical variables were compared with χ 2 statistic. Because of the nonrandomized nature of the study, a propensity-score adjusted analysis was performed to minimize any selection bias due to the differences in clinical characteristics between the 2 groups. Variables included in the logistic regression model to calculate the propensity-score were age, sex, diabetes, smoking, hypertension, hypercholesterolaemia, family history of coronary artery disease, acute coronary syndrome, prior MI, prior PCI, prior coronary artery bypass graft, left ventricular ejection fraction and multivessel disease. The C-statistic was 0.63, and the Hosmer–Lemeshow test p value was 0.31, confirming good discrimination and calibration of the propensity-score model. The individual propensity-score was incorporated into Cox proportional hazards regression models as a covariate as well as stent generation as the variable of interest to calculate the adjusted hazard ratio (HR). Furthermore, multivariable Cox proportional-hazards regression modeling of the entire population was also performed to determine independent predictors of MACE and TVR, using purposeful selection of covariates. Variables associated at univariate analysis with MACE (all with a p value < 0.1) and those judged to be of clinical importance from previous published literature were eligible for inclusion into the multivariable model-building process. The final multivariable model for this analysis included diabetes, sex, ejection fraction, presence of true bifurcation, use of final balloon kissing inflation, one- vs. two-stent strategy, stent length and stent type.
3
Results
Baseline clinical characteristics are summarized in Table 1 . Although the two groups were reasonably well-matched some differences were noted between the two populations, likely a reflection of the different recruitment periods. More specifically, there was a higher incidence of prior PCI in the second-generation group (27.1% vs. 41.7%, p < 0.01) as well as a trend towards a higher incidence of prior MI in the first-generation group (44.3% vs. 35.9%, p = 0.07).
| Patient characteristics | 1st generation DES (n = 273) | 2nd generation DES (n = 192) | P -value |
|---|---|---|---|
| Age (years) | 63.4 ± 11.1 | 64.3 ± 9.4 | 0.37 |
| Male sex | 232 (84.9%) | 159 (82.8%) | 0.53 |
| Ejection fraction (%) | 53.6 ± 9.2 | 54.8 ± 8.5 | 0.17 |
| Prior myocardial infarction | 121 (44.3%) | 69 (35.9%) | 0.07 |
| Prior percutaneous coronary intervention | 74 (27.1%) | 80 (41.7%) | < 0.01 |
| Prior coronary bypass surgery | 21 (7.7%) | 21 (10.9%) | 0.23 |
| Family history | 127 (46.5%) | 78 (40.6%) | 0.21 |
| Hypertension | 193 (70.7%) | 147 (76.6%) | 0.16 |
| Hypercholesterolemia | 180 (65.9%) | 137 (71.4%) | 0.22 |
| Multivessel disease | 181 (66.3%) | 111 (57.8%) | 0.14 |
| Current smoker | 52 (19.0%) | 23 (11.9%) | 0.04 |
| Diabetes | 70 (25.6%) | 58 (30.2%) | 0.28 |
| Diet controlled | 12 (17.2%) | 5 (8.6%) | 0.15 |
| Oral hypoglycemics | 37 (52.8%) | 33 (56.9%) | 0.59 |
| Insulin | 21 (30.0%) | 20 (34.5%) | 0.31 |
| Acute coronary syndrome | 88 (32.2%) | 54 (28.1%) | 0.34 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
