Abstract
Background
The optimal stent for use in saphenous vein graft (SVG) intervention is still debatable. Multiple randomized trials have compared drug-eluting stents (DES) to bare metal stents (BMS) in SVG interventions with conflicting results.
Methods
Authors searched the online databases for randomized controlled trials (RCTs) comparing DES to BMS in SVG percutaneous coronary interventions (PCI). We performed a meta-analysis using a random effects model to calculate the odds ratio for outcomes of interest.
Results
Authors studied six RCTs that included 1592 patients undergoing PCI of SVG. The mean follow up was 42 months. Patients mean age was the same in both groups: 70.3 years in the DES group (approximately 93.3% male) and 70.3 years in the BMS group (approximately 93.8% male). Vein graft age was 13.4 years in the DES PCI arm vs. 13.4 years in the BMS PCI arm. Four of the six trials reported data on embolic protection device use: 67% (303/452) in the DES arm vs. 67.9% (309/455) in the BMS arm. The primary outcome of long-term all-cause mortality was not different between DES vs. BMS (15.2% vs. 14.1%, OR 1.12, 95% CI 0.67–1.88; P = 0.66). Secondary outcomes were also similar between DES and BMS: major adverse cardiovascular events (31.6% vs. 33.1%, OR 0.79, 95% CI 0.45–1.38; P = 0.41); cardiac death (9% vs. 8.6%, OR 1.12, 95% CI 0.55–2.30; P = 0.75); myocardial infarction (8% vs. 9.5%, OR 0.84, 95% CI 0.47–1.51; P = 0.57); target lesion revascularization (16.4% vs. 14.4%, OR 0.98, 95% CI 0.50–1.92; P = 0.95); and target vessel revascularization (19% vs. 19.4%, OR 0.75, 95% CI 0.41–1.34; P = 0.33).
Conclusion
At a mean follow-up of 42 months, no difference was observed in clinical outcomes between DES and BMS in SVG interventions.
Highlights
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DES results in similar outcomes as BMS in SVG PCI up to 42 months of mean follow up.
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SVG PCI results in excess of 32% major adverse cardiovascular outcomes at 42 months.
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Post CABG patients who undergo SVG PCI have a mortality rate of 15% at 42 months.
1
Introduction
Percutaneous coronary interventions (PCI) for saphenous venous grafts (SVG) represent approximately 5–10% of all PCI procedures performed in United States [ , ] and have been shown to be an effective revascularization modality for patients presenting with significant SVG disease [ ]. However, the benefit of PCI in SVG failure is hampered by high rates of post-procedure complications, including in-stent restenosis (ISR) and major adverse cardiac events (MACE) [ ]. Drug-eluting stents (DES) have been shown to be more effective in reducing restenosis rates and therefore the need for subsequent revascularization when compared to bare metal stents (BMS) after native coronary intervention [ ]. However, it is unclear whether DES improve outcomes when compared with BMS in a subset of patients with SVG lesions.
Both randomized clinical trials and real world registries have compared the safety and effectiveness of DES versus BMS in SVG revascularization and demonstrated mixed results [ ]. This could be partially due to the fact that while the mechanism for ISR in native coronary arteries is primarily neointimal proliferation [ , ], SVG ISR is more complicated and has been reported to be a result of intimal hyperplasia, inward remodeling, and thrombus formation [ ].
The aim of the current meta-analysis is to review and analyze all published prospective randomized controlled trials (RCTs) comparing DES to BMS in the treatment of SVG obstructive lesions.
2
Methods
2.1
Study search and eligibility criteria
The current study follows the general guidelines of the Cochrane handbook (version 5.1.0) for systematic reviews of interventions. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analyses of Observational Studies in Epidemiology (MOOSE) statements for reporting systematic reviews [ , ] were used and a comprehensive search of the online databases was performed. PubMed, the National Institutes of Health Clinical Trials registry, and the Cochrane Central Register of Controlled Trials for RCTs were searched to compare DES to BMS in PCI of SVG.
Two independent researchers (M.S. and R.N.) performed the literature search of the online databases through June 2018. The initial search was performed using the following keywords: saphenous vein graft; saphenous vein graft percutaneous coronary intervention; drug-eluting stent saphenous vein graft; bare metal stent saphenous vein graft; post-coronary artery bypass graft percutaneous coronary intervention; and saphenous vein percutaneous coronary intervention both separately and in combination, and was restricted to the English language. Articles related to the topic were reviewed as were bibliography lists to identify further studies not revealed with the initial search. Abstracts in major meetings were also reviewed for possible studies that met the inclusion criteria. Studies were included in the final analysis if they compared DES to BMS in SVG PCI and reported outcomes at ≥12 months’ follow-up.
2.2
Data extraction
Four independent reviewers (M.S., R.N., H.S., and A.D.) extracted baseline study characteristics, patients’ demographic information, and clinical outcomes of interest from the retrieved studies. Any discrepancy was resolved by author consensus. The number of events for clinical outcomes in both arms was tabulated at the longest follow-up available.
2.3
Quality assessment
Quality assessment was performed at both study- and outcome levels. Quality of the included studies was assessed using the Newcastle-Ottawa Scale for cohort studies [ ]. We further used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool to assess quality of evidence at each outcome level as recommended by the Cochrane Handbook for Systematic Reviews of Interventions. This tool specifies four levels of quality (high, moderate, low, and very low) depending on the study types included in the assessment of each outcome.
2.4
Outcomes
The primary outcome of interest was long-term all-cause mortality. Secondary outcomes of interest were long-term major adverse cardiovascular events (MACE), cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), and target vessel revascularization (TVR).
2.5
Statistical analysis
All analyses were performed using Cochrane RevMan software (version 5.3). Random-effects summary odds ratios (ORs) using the DerSimonian and Laird model were performed [ ]. Confidence intervals (CIs) were calculated at 95% level for overall estimates effect. Heterogeneity was defined as I 2 > 50% and χ 2 P value < 0.01 [ ]. Weighted mean follow-up durations for outcomes were calculated using sample size as the weight. Publication bias was assessed using the funnel plot and Egger test [ ]. P-values were 2-tailed and were considered statistically significant if <0.05.
2
Methods
2.1
Study search and eligibility criteria
The current study follows the general guidelines of the Cochrane handbook (version 5.1.0) for systematic reviews of interventions. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analyses of Observational Studies in Epidemiology (MOOSE) statements for reporting systematic reviews [ , ] were used and a comprehensive search of the online databases was performed. PubMed, the National Institutes of Health Clinical Trials registry, and the Cochrane Central Register of Controlled Trials for RCTs were searched to compare DES to BMS in PCI of SVG.
Two independent researchers (M.S. and R.N.) performed the literature search of the online databases through June 2018. The initial search was performed using the following keywords: saphenous vein graft; saphenous vein graft percutaneous coronary intervention; drug-eluting stent saphenous vein graft; bare metal stent saphenous vein graft; post-coronary artery bypass graft percutaneous coronary intervention; and saphenous vein percutaneous coronary intervention both separately and in combination, and was restricted to the English language. Articles related to the topic were reviewed as were bibliography lists to identify further studies not revealed with the initial search. Abstracts in major meetings were also reviewed for possible studies that met the inclusion criteria. Studies were included in the final analysis if they compared DES to BMS in SVG PCI and reported outcomes at ≥12 months’ follow-up.
2.2
Data extraction
Four independent reviewers (M.S., R.N., H.S., and A.D.) extracted baseline study characteristics, patients’ demographic information, and clinical outcomes of interest from the retrieved studies. Any discrepancy was resolved by author consensus. The number of events for clinical outcomes in both arms was tabulated at the longest follow-up available.
2.3
Quality assessment
Quality assessment was performed at both study- and outcome levels. Quality of the included studies was assessed using the Newcastle-Ottawa Scale for cohort studies [ ]. We further used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tool to assess quality of evidence at each outcome level as recommended by the Cochrane Handbook for Systematic Reviews of Interventions. This tool specifies four levels of quality (high, moderate, low, and very low) depending on the study types included in the assessment of each outcome.
2.4
Outcomes
The primary outcome of interest was long-term all-cause mortality. Secondary outcomes of interest were long-term major adverse cardiovascular events (MACE), cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), and target vessel revascularization (TVR).
2.5
Statistical analysis
All analyses were performed using Cochrane RevMan software (version 5.3). Random-effects summary odds ratios (ORs) using the DerSimonian and Laird model were performed [ ]. Confidence intervals (CIs) were calculated at 95% level for overall estimates effect. Heterogeneity was defined as I 2 > 50% and χ 2 P value < 0.01 [ ]. Weighted mean follow-up durations for outcomes were calculated using sample size as the weight. Publication bias was assessed using the funnel plot and Egger test [ ]. P-values were 2-tailed and were considered statistically significant if <0.05.
3
Results
3.1
Characteristics of the included studies and patient cohorts
Six RCTs, with a total of 1592 patients, met the inclusion criteria and were included in the analysis [ ]. The search process is detailed in Fig. 1 . Patient mean age was the same in both groups: 70.3 years in the DES group (approximately 93.3% male) and 70.3 years in the BMS group (approximately 93.8% male). Indication for PCI was acute coronary syndrome in 46.2% in the DES arm and 48.1% in the BMS arm. Vein graft age was 13.4 years in the DES PCI arm vs. 13.4 years in the BMS PCI arm. Four out of the six trials reported data on embolic protection device use: 67% (303/452) in the DES arm vs. 67.9% (309/455) in the BMS arm. Characteristics of the included cohort are detailed in Table 1 .
