Abstract
Background
Everolimus-eluting stent (EES) implantation was superior to paclitaxel-eluting stent (PES) implantation for treatment of de-novo coronary artery disease. We evaluated the outcome of EES compared with PES for treatment of restenosis in bare-metal and drug-eluting stents (DES).
Methods and Materials
In a prospective observational study patients with in-stent restenosis (ISR) were treated with EES (N = 91) or PES (N = 107). Dual antiplatelet therapy was given for 6 months. Patients were scheduled for 6 months angiographic follow-up and 24 months clinical follow-up. Primary outcome measure was the occurrence of major adverse cardiac events (MACE) defined as a composite of cardiac death, any myocardial infarction and target lesion revascularization (TLR).
Results
Baseline data showed some differences between groups including frequency of DES restenosis, length of stented segment and reference vessel diameter. For EES versus PES occurrence of MACE (18.7% vs. 15.0%, p = 0.48) and need for TLR did not differ (13.2% vs. 9.3%, p = 0.39). In-stent late loss was similar with 0.20 ± 0.39 mm for EES and 0.18 ± 0.31 mm for PES (p = 0.34). Binary angiographic restenosis rate for the total segment was 18.0% and 16.7% (p = 0.85), respectively. In multivariable analysis the stented length (p = 0.014), minimal lumen diameter post stenting (p < 0.01) and repeated restenosis (p < 0.001) were risk factors for a higher late loss but not type of DES or presence of diabetes mellitus.
Conclusions
In this observational registry treatment of DES and BMS restenosis with EES versus PES implantation resulted in similar clinical and angiographic outcome.
For de-novo coronary artery disease everolimus-eluting stent (EES) implantation was superior to paclitaxel eluting stent (PES) implantation in terms of repeat revascularization and occurrence of stent thrombosis . Percutaneous coronary intervention (PCI) of in-stent restenosis (ISR) is associated with a high recurrence rate for repeat revascularizations. No data are available comparing EES with PES for treatment of ISR. The aim of this observational registry was to evaluate the angiographic and clinical outcome of EES compared with PES implantation for ISR treatment.
1
Methods
Patients with restenosis in bare-metal stents (BMS) or drug-eluting stents (DES) were consecutively treated with paclitaxel-eluting Taxus stents (PES; Boston Scientific, Natick, Massachusetts, USA) or everolimus-eluting Xience V stents (EES; Xience V, Abbott Vascular, Santa Clara, Calif, USA). Patients were anticoagulated with unfractionated heparin with an initial bolus of 70 U/kg, with subsequent boluses targeted to an activated clotting time of 200–250 s. Reference diameter was 2.25–4.0 mm allowing treatment with PES and EES. Treatment strategy was to cover the stenotic segment with one or more stents. High-pressure implantation with at least 14 bars was mandatory to ensure a proper alignment of stent struts at the vessel wall and to achieve a residual diameter stenosis of less than 20%. Dual antiplatelet therapy with acetylsalicylic acid 100 mg per day and clopidogrel 75 mg per day was prescribed for 6 months. Patients were scheduled for clinical and angiographic 6 months follow-up. Thereafter clinical follow-up was performed after 12 and 24 months.
Primary objective was the occurrence of major adverse cardiac events (MACE) defined as a composite of cardiac death, occurrence of myocardial infarction and target lesion revascularization (TLR). Secondary angiographic endpoint was in-stent late loss. Definite stent thrombosis was defined according to the ARC criteria . The study was ethically approved and all patients gave written informed consent.
1.1
Quantitative coronary angiography
Coronary angiography of the culprit lesion was performed in the same projections after intracoronary application of glycerol-trinitrate before and after stent implantation and at follow-up. Angiographic measurements were done with the CAAS 5.7 software (Pie Medical Imaging, Maastricht, The Netherlands) . Quantitative coronary measurements were performed blinded to clinical data at the University of Ulm, Germany. Measurements were performed for the stented segment, within 5 mm proximal and distal to the stent, and within the total segment. The total segment includes the stented segment plus the proximal and distal 5 mm segment to the stent. Restenosis was defined as diameter stenosis of more than 50%. Acute gain was calculated as the difference between minimal lumen diameter (MLD) post intervention and MLD pre stenting. Late loss was calculated as the difference between MLD post intervention and MLD at 6 months.
1.2
Statistical analysis
Categorical parameters are presented as counts and percentages. Comparison of proportions was done with Chi-square test. Continuous variables are presented as mean ± one standard deviation. Continuous variables for 2 groups were compared with the unpaired U test. Data are also given for the subgroup of patients with diabetes mellitus. Time-to-event data are shown as Kaplan–Meier curves and compared with the log-rank test. Multivariable regression analysis for MACE and in-stent late loss was performed including the following variables: diabetes, history of smoking, severe calcification, repeated restenosis, renal failure, length of stented segment, in-stent MLD post stenting, EES versus PES and BMS restenosis versus DES restenosis. Statistics were calculated with Statistica release 7.1 (StatSoft Inc., Tulsa, OK, USA).
2
Results
Patients with ISR (N = 198) were treated with PES (N = 107) or EES (N = 91). There was a high frequency of diabetes mellitus with 33% in EES and 45% in PES treated patients. Clinical and angiographic baseline parameters were similar between groups ( Tables 1 and 2 ) except for history of smoking and frequency of DES restenosis. Procedural data are detailed in Table 3 . Length of the stented segment was significantly longer with EES compared with PES stents. Balloon to artery ratio and final reference vessel diameter were significantly larger in the EES group compared with the PES group. Acute gain and final MLD in the stented and total segment did not differ.
| Everolimus eluting stent | Paclitaxel eluting stent | P Value | |
|---|---|---|---|
| Number of patients | 91 | 107 | |
| Age, years | 64.1 ± 10.6 | 67.4 ± 9.7 | 0.06 |
| Male sex, N (%) | 75 (82.4) | 83 (77.6) | 0.40 |
| Hypertension, N (%) | 71 (78.0) | 88 (82.2) | 0.46 |
| Hyperlipidemia, N (%) | 69 (75.8) | 93 (86.9) | 0.44 |
| History of smoking, N (%) | 46 (50.6) | 32 (29.9) | 0.003 |
| Diabetes mellitus, N (%) | 33 (36.3) | 45 (42.1) | 0.41 |
| Renal insufficiency, N (%) | 10 (11.0) | 15 (14.0) | 0.46 |
| Body mass index, kg/m 2 | 28.0 ± 4.4 | 27.5 ± 3.7 | 0.63 |
| Number of diseased vessels | 2.4 ± 0.7 | 2.2 ± 0.8 | 0.10 |
| Stable angina, N (%) | 61 (67.0) | 60 (56.1) | 0.34 |
| Unstable angina, N (%) | 30 (33.0) | 47 (44.0) | 0.34 |
| Everolimus eluting stent | Paclitaxel eluting stent | P Value | |
|---|---|---|---|
| Number of Lesions | 96 | 114 | 0.09 |
| Target vessel, N (%) | 34 (35.4) | 61 (53.5) | |
| LAD | 14 (14.6) | 16 (14.0) | |
| CX | 38 (39.6) | 32 (28.1) | |
| RCA | 9 (9.4) | 4 (3.5) | |
| CABG | |||
| Restenosis, first N (%) | 71 (74.0) | 96 (84.2) | 0.07 |
| ≥ second | 25 (26.0) | 18 (15.8) | 0.07 |
| DES restenosis, N (%) | 43 (44.8) | 35 (30.7) | 0.04 |
| Lesion length, mm | 16.8 ± 13.3 | 16.1 ± 9.2 | 0.51 |
| Range | 3.7-84.4 | 3.5-54.7 | |
| Reference vessel diameter, mm | 2.65 ± 0.60 | 2.55 ± 0.55 | 0.24 |
| Stenosis, % of luminal diameter | 76.5 ± 15.5 | 75.8 ± 13.1 | 0.80 |
| Minimal lumen diameter, mm | 0.61 ± 0.40 | 0.62 ± 0.38 | 0.81 |
| Everolimus eluting stent | Paclitaxel eluting stent | P Value | |
|---|---|---|---|
| Stents per lesion, N | 1.6 ± 1.1 | 1.3 ± 0.6 | 0.12 |
| Length of stented segment, mm | 33.9 ± 26.0 | 25.9 ± 15.2 | 0.022 |
| Maximal inflation pressure, atm | 16.3 ± 2.4 | 16.6 ± 2.9 | 0.40 |
| High pressure implantation 14 atm, N (%) | 92 (95.8) | 106 (93) | 0.38 |
| Final reference-vessel diameter, mm | 2.94 ± 0.50 | 2.72 ± 0.44 | < 0.01 |
| Final minimal luminal diameter, mm | |||
| Total segment | 2.20 ± 0.50 | 2.10 ± 0.49 | 0.19 |
| In-stent segment | 2.55 ± 0.44 | 2.44 ± 0.40 | 0.11 |
| Final stenosis, % of luminal diameter | |||
| Total segment | 21.4 ± 10.0 | 19.5 ± 11.5 | 0.09 |
| In-stent segment | 13.0 ± 4.5 | 10.6 ± 5.3 | < 0.001 |
| Acute gain, mm | |||
| Total segment | 1.59 ± 0.55 | 1.47 ± 0.48 | 0.12 |
| In-stent segment | 1.94 ± 0.53 | 1.81 ± 0.42 | 0.16 |
2.1
Clinical follow-up
Clinical follow-up after 24 months was obtained in all 198 patients. The occurrence of MACE after 2 years did not differ between both groups with 18.7% (N = 17/91) with EES versus 15.0% (N = 16/107, p = 0.48) with PES ( Fig. 1 ). Furthermore there was no statistical difference for the single components of MACE with cardiac death (EES 1.1%, N = 1/91 versus PES 3.7%, N = 4/107, p = 0.24), myocardial infarction (EES 4.4%, N = 4/91 versus PES 1.9%, N = 2/107) and TLR (EES 13.2%, N = 12/91 versus PES 9.3%, N = 10/107, p = 0.39). Rate of definite (definite and probable) stent thrombosis was 1.1% (2.2%) for EES versus 0.0% (1.9%) for PES.
Multivariable regression analysis for occurrence of MACE showed that type of implanted DES (p = 0.69), presence of diabetes mellitus (p = 0.22), restenosis in BMS versus DES (0.23) and other factors except for treatment of repeated restenosis (p = 0.006) were not predictive.
2.2
Angiographic results
Angiographic follow-up rate was only 62% (N = 122/198) after median 190 days. In-stent late loss was almost similar between groups with 0.20 ± 0.39 mm for EES and 0.18 ± 0.31 mm for PES. Furthermore, late loss for the distal and proximal segment as well as for the total segment did not differ ( Table 4 ). Binary angiographic restenosis rate did not differ. The in-stent late loss for the EES population did not differ between patients with restenosis in PES versus -limus eluting stents with 0.26 ± 0.41 mm versus 0.28 ± 0.47 mm (p = 0.94). In patients without diabetes mellitus in-stent late loss was significantly lower with EES compared with PES (0.13 ± 0.31 mm versus 0.20 ± 0.33 mm, p = 0.047). In patients with diabetes mellitus in-stent late loss was higher with EES compared with PES (0.36 ± 0.49 mm versus 0.14 ± 0.27 mm, p = 0.25; interaction p-value for diabetes with treatment p = 0.03). Multivariable regression analysis for in-stent late loss showed that length of stented segment (p = 0.013), MLD post stenting (p < 0.01) and treatment of repeated restenosis (p < 0.001) were significant predictors for in-stent late loss but not presence of diabetes mellitus or type of implanted stent.
