Saphenous vein grafts (SVGs) are prone to an aggressive atherosclerotic process, and the efficacy of drug-eluting stents (DES) in treating this is still debated. In recent years, second-generation DES have been increasingly used in SVG intervention. The main objective of this study was to compare midterm clinical outcomes between first- and second-generation DES in SVGs because data regarding the use of second-generation DES in SVG are lacking. Patients treated with first-generation DES (127 patients with 143 lesions) and those treated with second-generation DES (84 patients with 100 lesions) were included in the study. Major adverse cardiac events, defined as the composite of all-cause death, myocardial infarction, and target vessel revascularization, as well as target vessel revascularization and target lesion revascularization separately, were evaluated at 30-day, 12-month, and 18-month follow-up. Baseline characteristics were similar between the 2 groups. Older grafts were treated with second-generation DES (11.6 ± 5.3 vs 14.3 ± 6.0 years, p = 0.001). Stent length was longer in the first-generation group (34.1 ± 25.1 vs 30.5 ± 19.4 mm, p = 0.006), and maximum balloon diameter was smaller in the second-generation group (3.42 ± 0.42 vs 3.30 ± 0.41 mm, p = 0.003). Embolic protection device use was higher in the second-generation DES group (55.2% vs 72.0%, p = 0.012). At 18-month follow-up, rates of major adverse cardiac events, target vessel revascularization, and target lesion revascularization for the first- and second-generation groups were 24.4% versus 20.2% (p = 0.479), 18.1% versus 14.2% (p = 0.465), and 15.0% versus 10.7% (p = 0.373), respectively. In conclusion, second-generation DES are at least comparable with first-generation DES with regard to clinical outcomes at midterm follow-up.
Saphenous vein grafts (SVG) are the most common type of graft used in coronary artery bypass graft surgery. Graft attrition rate, however, is high, at 15% at 1 year and up to 45% at 5 years, and with the risks of repeat surgery not being negligible, percutaneous coronary intervention (PCI) is the preferred treatment when revascularization is indicated. SVG interventions represent 6% to 15% of all PCIs, a figure that may increase given some evidence that SVG stenoses of 30% to 60% may benefit from stent implantation. Small, randomized trials and subsequent meta-analyses comparing drug-eluting stents (DES) to bare-metal stents (BMS) in SVG PCI have favored the use of DES in this setting. In the largest randomized trial, Is Drug-Eluting Stenting Associated With Improved Results in Coronary Artery Bypass Grafts? (ISAR-CABG), DES were found to be superior to BMS with regard to major adverse cardiac events (MACEs) and ischemia-driven target lesion revascularization (TLR) and target vessel revascularization (TVR). However, other smaller trials failed to show similar benefits. A previous study by our group comparing clinical outcomes at 2 years in patients with SVG PCI with either BMS or first-generation DES suggested that the latter were associated with reduced revascularization rates. In recent years and with the evolution of stent technology, newer generation DES have been used for the treatment of SVG disease. To date, however, there are no published data, to our knowledge, with regard to their safety and efficacy at short-term and midterm follow-up. Here, we report and compare short-term and midterm clinical outcomes in patients who underwent SVG PCI with either first- or second-generation DES at 2 high-volume centers in Milan, Italy.
Methods
All consecutive patients successfully treated with paclitaxel-eluting stents or sirolimus-eluting stents from April 2002 to March 2006, as well as consecutive patients successfully treated with either everolimus-eluting or zotarolimus-eluting stents from January 2005 to April 2011 in whom 18-month follow-up was available were included in the study. We thus identified 127 consecutive patients (with 143 lesions) who underwent percutaneous revascularization of SVG lesions with first-generation DES (the first-generation DES group) and 84 consecutive patients (with 100 lesions) with second-generation DES (the second-generation DES group). Patients were excluded if any of the following were present: acute myocardial infarction <1week before the index procedure, implantation of a covered stent, or inability to cross the lesion with a guidewire. All patients provided informed consent for the procedure and subsequent data collection and analysis for research purposes. Diabetes mellitus was defined as fasting blood glucose >126 mg/dl, self-reported diabetes, or treatment with antidiabetic medications. Hypercholesterolemia was defined as total serum cholesterol >240 mg/dl, self-reported history of hypercholesterolemia, or current lipid-lowering treatment. Hypertension was defined as previously documented systolic blood pressure >140 mm Hg and/or diastolic blood pressure >80 mm Hg, self-reported history of hypertension, or treatment with antihypertensive medication. All patients were pretreated with aspirin and either ticlopidine or clopidogrel. A 300- or 600-mg loading dose of clopidogrel before the index procedure was administered if a patient was not pretreated. Intravenous heparin was administered to maintain an activated clotting time >250 seconds during the procedure. Platelet glycoprotein IIb/IIIa receptor inhibitors, an interventional approach, and intravascular ultrasound were used at the operator’s discretion. After the procedure, all patients were prescribed lifelong aspirin therapy and clopidogrel or ticlopidine for ≥6 or 12 months.
Clinical follow-up was performed by clinic visit or by telephone interview. Because of the different time periods in which stents were implanted in the 2 groups and the resultant marked difference in clinical follow-up duration available, we censored events occurring after 18 months in the 2 groups. Clinical outcomes reported represent patient-specific data unless otherwise stated. The measured end points were MACEs, defined as composite of all-cause death, myocardial infarction (including periprocedural), and TVR. Death was considered cardiac in origin unless obvious noncardiac causes were identified. We defined postprocedural non-Q-wave myocardial infarction as a creatinine kinase-MB elevation of >3 times the upper limit of normal. Creatinine kinase was routinely measured after PCI in all patients at the 2 centers. Nonprocedural or spontaneous MI was defined as an elevation of troponin above the upper range limit in combination with ≥1 of the following: symptoms of ischemia, electrocardiographic changes indicative of new ischemia, or the development of pathologic Q waves on electrocardiography. TLR was defined as repeat revascularization for the lesion in the previously treated segment or in the adjacent 5 mm. The occurrence of stent thrombosis was defined on the basis of the Academic Research Consortium definition. A chronic total occlusion was defined as complete occlusion with Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 lasting ≥3 months. The ejection fraction was defined as normal if >55%. Procedural success was defined as completion of the procedure with no in-laboratory complications, final TIMI flow grade 3, and residual stenosis <20%.
Continuous variables are presented as mean ± SD or as median (interquartile range) and categorical variables as frequency (percentage). Continuous variables were compared using Mann-Whitney U tests. Categorical variables were compared using chi-square tests. Multivariate Cox proportional-hazards regression modeling was performed to determine the independent predictors of MACEs, using purposeful selection of covariates. Variables associated on univariate analysis with MACEs (all with p values <0.10) and those judged to be of clinical importance from previous published research were eligible for inclusion in the multivariate model-building process. Candidate variables included age, gender, stent type, diabetes, left ventricular ejection fraction, graft age, glycoprotein IIb/IIIa inhibitor use, embolic protection device use, stent diameter, and stent length. The final model included graft age, diabetes, stent size, and stent type.
Results
Baseline clinical characteristics are listed in Table 1 . Patients who received second-generation DES tended to be older (67.6 ± 8.3 vs 69.4 ± 9.6 years, p = 0.081) and showed a tendency toward a higher prevalence of hypertension (66.9% vs 78.6%, p = 0.066) compared with the first-generation DES group. There was no difference in the prevalence of diabetes between the 2 groups (33.1% vs 32.1%, p = 0.888). Overall, the 2 groups had lower than normal left ventricular ejection fractions (49.0 ± 9.1% vs 48.6 ± 10.7%, p = 0.368), probably a result of the high incidence of previous myocardial infarction in the 2 groups (60.6% vs 57.1%, p = 0.614).
| Clinical Characteristic | First-Generation DES (n = 127) | Second-Generation DES (n = 84) | p Value |
|---|---|---|---|
| Age (yrs) | 67.6 ± 8.3 | 69.4 ± 9.6 | 0.081 |
| Men | 113 (89.0%) | 78 (92.9%) | 0.346 |
| Previous PCI | 58 (45.7%) | 48 (57.1%) | 0.104 |
| Previous myocardial infarction | 77 (60.6%) | 48 (57.1%) | 0.614 |
| Hypertension | 85 (66.9%) | 66 (78.6%) | 0.066 |
| Hypercholesterolemia | 99 (78.0%) | 66 (78.6%) | 0.915 |
| Current or former smokers | 58 (45.7%) | 43 (51.2%) | 0.464 |
| Diabetes mellitus | 42 (33.1%) | 27 (32.1%) | 0.888 |
| Diet controlled | 2 (1.6%) | 1 (1.2%) | 0.767 |
| Oral hypoglycemic medications | 27 (21.3%) | 14 (16.7%) | 0.409 |
| Insulin | 13 (10.2%) | 12 (14.3%) | 0.373 |
| Left ventricular ejection fraction (%) | 49.0 ± 9.1 | 48.6 ± 10.7 | 0.368 |
| No. of SVGs treated per patient | 0.867 | ||
| 1 | 123 (96.8%) | 81 (96.4%) | |
| 2 | 4 (3.2%) | 3 (3.6%) | |
| No. of narrowings treated per patient | 0.136 | ||
| 1 | 111 (87.4%) | 67 (79.8%) | |
| 2 | 16 (12.6%) | 17 (20.2%) |
Procedural characteristics are listed in Table 2 . There were no significant differences in the location of lesion treated or native vessel grafted between the 2 groups. Older grafts were treated in the second-generation DES group (11.6 ± 5.3 vs 14.3 ± 6.0 years, p = 0.001). With regard to stent characteristics, stent length was longer in the first-generation group (34.1 ± 25.1 vs 30.5 ± 19.4 mm, p = 0.006), and maximum balloon diameter was smaller in the second-generation group (3.42 ± 0.42 vs 3.30 ± 0.41 mm, p = 0.003). Embolic protection devices were used more frequently in the second-generation DES group (55.2% vs 72.0%, p = 0.012). In the first-generation DES group, sirolimus-eluting stents were more commonly used than paclitaxel-eluting stents (62.2% vs 37.8%, p = 0.003). Zotarolimus-eluting stents (48.0%) and everolimus-eluting stents (52.0%) were the stents of choice in the second-generation DES group.
| Characteristic | First-Generation DES (grafts = 131, lesions = 143) | Second-Generation DES (grafts = 100, lesions = 100) | p Value |
|---|---|---|---|
| Years SVG in place | 11.6 ± 5.3 | 14.3 ± 6.0 | 0.001 |
| Recipient native coronary artery territory | 0.368 | ||
| SVG to LAD/diagonal | 45 (34.4%) | 26 (26.0%) | |
| SVG to LC/OM | 52 (39.7%) | 42 (42.0%) | |
| SVG to right/PDA | 34 (26.0%) | 32 (32.0%) | |
| Sequential grafts | 18 (13.7%) | 18 (18.0%) | 0.242 |
| Location of lesion | 0.705 | ||
| Ostial | 32 (22.4%) | 26 (26.0%) | |
| Proximal | 37 (25.9%) | 20 (20.0%) | |
| Mid | 36 (25.2%) | 24 (24.0%) | |
| Distal and anastomotic | 38 (26.6%) | 30 (30.0%) | |
| Lesion characteristics | |||
| Restenotic lesions | 34 (23.8%) | 18 (18.0%) | 0.829 |
| Total occlusion | 11 (7.7%) | 5 (5.0%) | 0.832 |
| Procedural characteristics | |||
| Direct stenting | 32 (22.4%) | 23 (23.0%) | 0.290 |
| No. of stents per lesion | 1.34 ± 0.80 | 1.384 ± 0.65 | 0.848 |
| Mean stent length per lesion (mm) | 34.1 ± 25.1 | 30.5 ± 19.4 | 0.006 |
| Stent diameter (mm) | 3.32 ± 0.38 | 3.22 ± 0.39 | 0.052 |
| Maximum balloon diameter (mm) | 3.42 ± 0.42 | 3.30 ± 0.41 | 0.003 |
| Maximum balloon inflation pressure (atm) | 17.7 ± 4.7 | 17.3 ± 6.2 | 0.113 |
| Embolization protection devices | 79 (55.2%) | 72 (72.0%) | 0.012 |
| Distal occlusion | 10 (7.0%) | 13 (13.0%) | |
| Distal filter | 62 (43.4%) | 47 (47.0%) | |
| Proximal occlusion | 7 (4.9%) | 12 (12.0%) | |
| Glycoprotein IIb/IIIa inhibitor use | 31 (21.7%) | 17 (17.0%) | 0.369 |
Clinical outcomes at 30 days, 12 months, and 18 months are listed in Table 3 . The cumulative rate of MACEs, myocardial infarction, TLR, and TVR was similar in the 2 groups at 12 months after stent implantation. No statistical difference was noted at 18 months between the first- and second-generation groups with regard to TVR (18.1% vs 14.2%, p = 0.465), TLR (per patient; 15.0% vs 10.7%, p = 0.373), and MACEs (24.4% vs 20.2%, p = 0.479). Multivariate Cox regression analysis was used to identify independent predictors of MACEs. The final multivariate model included graft age, diabetes, stent size, and stent type. The only significant predictor of MACEs, driven largely by TVR, during the 18-month follow-up period was diabetes (hazard ratio 2.42, 95% confidence interval 1.29 to 4.56, p = 0.006). Regarding TLR according to stent type, this was more frequent with sirolimus-eluting stents than everolimus-eluting stents (15.7% vs 7.7%), although this did not reach statistical significance (p = 0.168; Table 4 ). No significant differences were noted between the 2 groups in all-cause and cardiac death (all-cause death 10 [7.9%] vs 4 [4.8%], p = 0.374; cardiac death 7 [5.5%] vs 3 [3.6%], p = 0.516). According to the Academic Research Consortium definition of stent thrombosis, the rate of definite or probable stent thrombosis was 1.2% in the second-generation group and 0.8% in the first-generation group at 18 months. The stent thrombosis in the second-generation group was subacute with an everolimus-eluting stent at 23 days after the procedure (patients receiving dual-antiplatelet therapy). In the first-generation group, the single case of stent thrombosis occurred with a paclitaxel-eluting stent at 431 days after the procedure (antiplatelet therapy was stopped for a surgical procedure).
