This meta-analysis was undertaken to assess the efficacy and safety of drug-eluting stents (DESs) compared to bare metal stents (BMSs) in saphenous vein graft (SVG) interventions. DESs decrease the risk of target vessel revascularization in native coronary arteries compared to BMSs. The ideal treatment strategy in patients with SVG disease is unknown. A search of the published reports was conducted to identify studies that compared DESs and BMSs in SVG intervention with a minimum follow-up of 6 months. A total of 19 studies (2 randomized trials and 17 registries), including 3,420 patients who had undergone SVG intervention (DESs, n = 1,489 and BMS, n = 1,931), met the selection criteria. The mean length of follow-up was 20 ± 12 months. Using the fixed effect model, target vessel revascularization was less frequently performed in patients who had undergone SVG intervention with a DES than with a BMS (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.49 to 0.72). The incidence of myocardial infarction was lower in patients with a DES than in those with a BMS (OR 0.69, 95% CI 0.49 to 0.99). No differences were found in the risk of death (OR 0.78, 95% CI 0.59 to 1.02) or stent thrombosis (OR 0.41, 95% CI 0.15 to 1.11) between the 2 groups. In conclusion, these findings support the use of DESs in SVG lesions.
Although the advantage of drug-eluting stents (DESs) versus bare metal stents (BMSs) has been well documented for native coronary artery disease, data are limited for the systematic evaluation of DESs and BMSs in saphenous vein graft (SVG) disease. The clinical studies undertaken to evaluate DESs in SVG were underpowered, and the results of these studies were inconsistent with respect to the rates of major adverse cardiac events, death, myocardial infarction (MI), and target vessel revascularization (TVR). The results of the only 2 randomized clinical trials evaluating DESs and BMSs in SVG disease were also disparate, with one showing greater mortality with sirolimus-eluting stents at long-term follow-up. Therefore, to determine the safety and efficacy of DESs in SVG intervention, we undertook the present meta-analysis of all published randomized controlled trials and observational studies comparing DESs and BMSs to treat SVG disease.
Methods
A data search of the MEDLINE, EMBASE, and Cochrane databases from January 2003 to February 2009 was conducted using the keywords “percutaneous coronary intervention,” “saphenous vein graft,” “drug-eluting stent,” “sirolimus-eluting stent,” and “paclitaxel-eluting stent.”
The studies to be included in the analysis were reviewed for acceptability using predefined inclusion criteria. Randomized clinical trials and observational studies were included if they had been published in peer-reviewed journals, with the full text available in English; had compared sirolimus-eluting stents (Cypher, Cordis/Johnson & Johnson, Warren, New Jersey) and/or paclitaxel-eluting stents (Taxus Express, Boston Scientific, Natick, Massachusetts; and V-Flex Plus, Cook, West Lafayette, Indiana) with BMSs for SVG intervention; and had had a length of follow-up of ≥6 months after the index SVG intervention.
Two independent reviewers (MSL and TY) extracted the following data: the first author of the study, baseline demographic and procedural data, sample size, length of follow-up, and clinical events (death, MI, and TVR). The results of the Death and Events at Long-term follow-up AnalYsis: Extended Duration of the Reduction of restenosis in saphenous vein grafts with Cypher stent (DELAYED RRISC) trial were used because the length of follow-up was longer than the follow-up in the Reduction of Restenosis In Saphenous vein grafts with Cypher sirolimus-eluting stent (RRISC) trial.
The primary end point was TVR, which was defined as subsequent percutaneous or surgical revascularization of the target vessel. The secondary end points were death, MI, and stent thrombosis.
All meta-analyses were done using the Comprehensive Meta-Analysis system, version 2.2 (Biostat, Inc., Englewood, New Jersey). A fixed effect model of meta-analysis was used to aggregate the study level data. In addition, a random effects model was used for reference. Forest plots were generated for the graphic presentations, and Q-statistics were computed for test of heterogeneity across the different studies. For each study and all studies overall, the odds ratios (ORs) and their associated confidence intervals (CIs) were calculated according to the event rates for comparing DES and BMS patients.
The aggregate baseline characteristics were computed using weighted means and standard deviations for continuous variables and the weighted proportions for the binary variables according to the availability of the data in each study arm. The p values for the 2-group comparisons of baseline covariates were calculated using a 2-sample t test for continuous data and the chi-square test for categorical data in Microsoft Excel (Microsoft, Redmond, Washington) as ancillary software.
Results
The 19 studies that met the selection criteria included 2 randomized controlled trials (Stenting of Saphenous Vein Grafts [SOS] and RRISC trials) and 17 registries. A total of 1,489 patients underwent SVG intervention with DESs and 1,931 patients with BMSs.
The clinical characteristics are listed in Table 1 . Several differences were present in the baseline characteristics owing to the limitation of observational studies and the increase in the power of the test by the aggregate sample size. The DES group was older (70.0 vs 69.3 years, p = 0.02), had fewer patients who were smoking (31% vs 35%, p = 0.03), more diabetic patients (37% vs 33%, p = 0.001), more patients with hypercholesterolemia (80% vs 74%, p <0.0001), and had a greater mean ejection fraction (48% vs 47%, p = 0.02), longer mean stent length (24 ± 11 vs 21 ± 9 mm, p <0.001), smaller mean stent diameter (3.1 ± 0.1 vs 3.6 ± 1.3 mm, p <0.001), more frequent use of distal embolic protection device (28% vs 23%, p = 0.01), and less frequent use of glycoprotein IIb/IIIa antagonists (24% vs 42%, p <0.001) than the BMS group. The mean length of follow-up was 20 ± 12 months (range 6 to 48). Of the 19 studies comparing DESs and BMSs, 12 included a combination of sirolimus-eluting and paclitaxel-eluting stents, 4 studies were exclusively of sirolimus-eluting stents, and 3 studies were exclusively of paclitaxel-eluting stents. Finally, Gioia et al reported ST-segment elevation MI only.
| Study | Patients (n) | Age (years) | Men (%) | DM (%) | Hypercholesterolemia (%) | Previous PCI (%) | EF (%) | Graft in Place (years) | Stent Length (mm) | Stent Diameter (mm) | DEP (%) | Follow-up (mo) | Type of DES |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Assali et al | 68/43 | 70/71 | 88/79 | 54/12 | 91/91 | NR/NR | 46/47 | 11/11 | 30.3/2020.7 | 3.3/3.6 | 38/48 | 24/24 | Cypher/Taxus |
| van Twisk et al | 122/128 | 68/69 | 84/80 | 31/21 | 66/45 | 30/27 | NR/NR | NR/NR | 32/31.9 | 3.1/3.5 | 1.6/4.7 | 48/48 | Cypher/Taxus |
| Okabe et al | 138/344 | 70/70 | 75/73 | 53/43 | 93/90 | 40/47 | 44/41 | 10/10 | 20.3/19.8 | 3.1/3.8 | 26/21 | 12/12 | Cypher/Taxus |
| BASKET | 34/13 | 71/71 | 79/100 | 29/17 | 79/92 | 44/39 | NR/NR | NR/NR | 41/46 | NR/NR | NR/NR | 18/18 | Cypher/Taxus |
| Kaplan et al | 37/33 | 72/71 | 92/91 | 16/24 | 60/42 | 65/61 | 48/52 | NR/NR | 18.9/15.6 | 3.4/3.7 | 27/33 | 12/12 | Cypher/Taxus |
| Gioia et al | 106/119 | 71/70 | 80/81 | 45/37 | 75/65 | 40/35 | 44/47 | 12/12 | 21/24 | 3.3/3.9 | NR/NR | 24/24 | Cypher/Taxus |
| Ramana et al | 141/170 | 70/69 | 81/88 | 52/42 | 94/89 | 61/51 | 47/45 | 12/13 | 28.3/2,029.3 | 3.3/4.2 | NR/NR | 31/36 | Cypher |
| Vignali et al | 72/288 | 73/71 | 74/85 | 29/24 | 59/59 | 30/19 | NR/NR | 9/11 | 19.7/18.7 | 3/3.5 | NR/NR | 12/12 | Cypher/Taxus |
| Bansal et al | 37/72 | 68/65 | NR/NR | 51/35 | 84/68 | NR/NR | NR/NR | NR/NR | 17.1/17.9 | 3/3.8 | 39/27 | 33/33 | Cypher/Taxus |
| Minutello et al | 59/50 | 71/69 | 71/80 | 48/44 | 75/74 | 32/28 | 48/48 | 13/9 | NR/NR | 3.1/3.4 | 71.2/48 | 20/20 | Cypher |
| Ellis et al | 175/175 | 70/69 | 76/79 | 39/39 | 91/89 | NR/NR | NR/NR | NR/NR | 20.6/2,021.6 | NR/NR | 35/25 | 12/12 | Cypher |
| RRISC | 38/37 | 73/72 | 82/89 | 16/14 | 87/84 | NR/NR | 68/72 | 12/13 | NR/NR | NR/NR | NR/NR | 31/32 | Cypher |
| Hoffman et al | 60/60 | 67/67 | 90/93 | 25/28 | 88/87 | NR/NR | NR/NR | 11/10 | 16.7/14.6 | 3.3/3.4 | 52/47 | 6/6 | Paclitaxel-eluting stent |
| Lee et al | 139/84 | 69/69 | 81/74 | 23/24 | 78/77 | NR/NR | 45/42 | 8/8 | NR/NR | 2.9/3.0 | 15/19 | 9/9 | Cypher/Taxus |
| Ge et al | 61/89 | 67/67 | 84/89 | 20/16 | 66/49 | NR/NR | 51/49 | 10/9 | 29.4/2,020.4 | 3.4/3.8 | 31/23 | 6/6 | Cypher/Taxus |
| SOS | 41/39 | 66/67 | 100/100 | 44/44 | 98/95 | NR/NR | NR/NR | 11/12 | 18/18 | 3.1/3.2 | 51/56 | 18/18 | Taxus |
| Lozano et al | 98/114 | 71/66 | 81/72 | 38/49 | 61/62 | 19/27 | 55/58 | 10/9 | 22/16 | 3/2.9 | NR/NR | 30/30 | Cypher/Taxus |
| Wohrle et al | 13/26 | 71/70 | 92/96 | 23/31 | 77/92 | NR/NR | NR/NR | 11/9 | 12.1/12.4 | 2.71/1.84 | NR/NR | 12/12 | Taxus |
| Guo et al | 50/47 | 74/71 | 56/55 | 24/30 | 80/68 | 34/40 | 51/49 | NR/NR | 22.1/18.8 | 2.76/3.03 | 4/0 | 12/12 | Cypher/Taxus |
The overall analysis under the fixed effect model revealed a 41% reduction in TVR in patients who underwent SVG intervention with DESs compared to BMSs (OR 0.59, 95% CI 0.49 to 0.72; Figure 1 ). The chi-square test with 18 degrees of freedom for the Q statistic was 49.85 (p = 0.0001), indicating that significant heterogeneity was present among the studies. The random effects model was therefore used to analyze the heterogeneity, and the result was consistent (OR 0.50, 95% CI 0.36 to 0.71). Hence, the result for the overall analysis was robust.
The present analysis revealed that patients who underwent SVG intervention with DESs had lower mortality by 22% compared to the mortality rate of the patients with BMSs (OR 0.78, 95% CI 0.59 to 1.02; Figure 2 ). The chi-square test with 17 degrees of freedom for the Q statistic was 15.17 (p = 0.58), indicating no significant heterogeneity among the studies.
The overall analysis under the fixed effect model revealed that patients who underwent SVG intervention with DESs had a lower risk of MI by 31% compared to BMS use (OR 0.69, 95% CI 0.49 to 0.99). The chi-square test with 14 degrees of freedom for the Q statistic was 26.11 (p = 0.03), indicating significant heterogeneity among the studies. The random effects model was therefore used to analyze the heterogeneity (OR 0.76, 95% CI 0.44 to 1.29; Figure 3 ).
