The incidence and predictors of major adverse cardiac events after percutaneous coronary intervention of saphenous vein grafts have not been evaluated in the era of routine embolic protection device (EPD) use and the current standards of antiplatelet therapy. The Assessment of the Medtronic AVE Interceptor Saphenous Vein Graft Filter System (AMEthyst) is the largest randomized trial of vein graft intervention comparing the Interceptor EPD and either the GuardWire or FilterWire EPD as the control. The baseline demographic, procedural, and clinical characteristics and the 30-day major adverse cardiac events ([MACE] death, myocardial infarction, and repeat revascularization [either surgery or percutaneous coronary intervention] of the target vessel) were recorded for 748 patients who had undergone vein graft intervention with distal embolic protection. At 30 days, MACE had occurred in 58 patients (7.8%). The univariate predictors of MACE at 30 days included plaque volume (odds ratio 1.005/mm 3 , p <0.0001), target lesion length (odds ratio 1.046/mm, p <0.001), vein graft degeneration score (odds ratio 1.631, p = 0.001), coronary narrowing classification (odds ratio 1.697, p = 0.004), reference vessel diameter (odds ratio 1.689, p = 0.004), and male gender (odds ratio 2.406, p = 0.046) and was independent of device type (p = 0.74). The plaque volume was the most important and only multivariate predictor of MACE. The highest quartile of plaque volume defined a subset at particular risk, despite EPD use (MACE 15.8% vs 5.0%, p <0.001). In conclusion, in a patient population in which EPD and preprocedure thienopyridine therapy were uniformly implemented, MACE occurred with an incidence of 7.8% at 30 days. An increasing plaque volume was the most important determinant of MACE and defined a population at particular risk.
Despite the use of embolic protection devices (EPDs), major adverse cardiac events (MACE) remain frequent after saphenous vein graft (SVG) percutaneous coronary intervention (PCI) with an incidence greater than after native coronary intervention (approximately 10%). Given the acute and long-term effects of MACE on survival, it is important to define the univariate and multivariate predictors of MACE in the current era of routine EPD use and preprocedure thienopyridine therapy. Furthermore, identifying patients at particular risk of MACE who might derive the greatest benefit from embolic protection would be helpful, given the current low use of EPDs. Assessment of the Medtronic AVE Interceptor Saphenous Vein Graft Filter System (AMEthyst) is the largest randomized controlled study evaluating mandated EPD use for SVG intervention. The AMEthyst trial most accurately reflects contemporary practice, because all patients received preprocedure thienopyridine therapy and most received a drug-eluting stent.
Methods
AMEthyst included 797 patients (813 lesions) with symptomatic ischemic heart disease due to obstructive disease (>50% diameter stenosis) of one SVG, randomized in a 2:1 fashion to either the Interceptor PLUS EPD (Medtronic Cardiovascular, Santa Rosa, California) or a control EPD (GuardWire, Medtronic, or FilterWire EZ, Boston Scientific, Boston, Massachusetts). Detailed descriptions of the AMEthyst study have been previously published. The major exclusion criteria included acute or recent (<24 hours) myocardial infarction, ejection fraction <25%, lesions requiring adjunctive atherectomy or debulking, and creatinine >2.5 mg/dl (if chronic hemodialysis was not required). PCI of ≤2 nontarget native coronary lesions was permitted during the index procedure. All patients received a loading dose of 325 mg of aspirin and either 300 mg of clopidogrel or 500 mg of ticlopidine, unless already receiving chronic thienopyridine therapy. The choice of a drug-eluting or bare metal stent and the use of a glycoprotein IIb/IIIa receptor inhibitor were left to the operator. The 30-day clinical outcomes were available for 748 patients (93.9%) who comprised the cohort used for the present patient-based analysis. The primary end point of the present study, 30-day MACE, was defined as a composite of death, myocardial infarction (defined as creatine kinase-MB elevation >3 times the upper limit of normal), or repeat revascularization (surgery or PCI) of the target vessel. An independent clinical events committee at Harvard Clinical Research Institute (Boston, Massachusetts) adjudicated all events, and quantitative coronary angiography was performed at an independent core laboratory (Brigham and Women’s Hospital Angiographic Core Laboratory, Boston, Massachusetts) using a standardized method.
The clinical, angiographic, and procedural variables were evaluated as potential predictors of MACE at 30 days. The clinical variables included patient age, gender, diabetes, current smoking, hypertension, previous stroke, unstable angina, previous myocardial infarction, ejection fraction <50%, and previous gastrointestinal bleeding. The angiographic variables included lesion length (“shoulder-to-shoulder” >20% lumen narrowing), reference vessel diameter, modified American College of Cardiology/American Heart Association coronary narrowing classification, lesion percentage of diameter stenosis, evidence of thrombus, vessel angulation of ≥45°, estimated lesion plaque volume, and SVG degeneration score. The estimated plaque volume was defined as π(lesion length)[(reference vessel diameter/2) 2 − (minimal lumen diameter/2) 2 ]. This variable equals the volume of a cylinder whose diameter equals the reference vessel diameter and whose length equals the lesion length, minus the volume of a cylinder of the same length, whose diameter equals the minimal lumen diameter within the lesion. The SVG degeneration score is an ordinal metric of the extent of lumen irregularities and ectasia (>20% of the reference normal segment) within the SVG that is <25% (SVG degeneration score 0), 25% to 50% (score 1), 51% to 75% (score 2), or >75% (score 3) of the total SVG length. The procedural variables included both the planned (assessed before the procedure) and actual use of a glycoprotein IIb/IIIa receptor inhibitor. Actual glycoprotein IIb/IIIa receptor inhibitor use was selected as the more clinically relevant variable for inclusion in the multivariate model. The multivariate model was adjusted for the type of EPD used (Interceptor PLUS vs control) to account for possible variations between the devices. The c-statistic was used to define the optimal model when the predictor sets were not inclusive.
Binary variables were compared using Fisher’s exact test and continuous variables, using Student’s t test. A p value = 0.05 was considered statistically significant for the comparisons of baseline variables between groups. Univariate logistic regression analysis was performed for the candidate clinical, angiographic, and procedural variables, with 30-day MACE as the outcome of interest. Multivariate logistic regression analysis was performed using a stepwise procedure that included all the angiographic, clinical, and procedural predictors, with 30-day MACE as the dependent variable. A significance level of 0.2 was used for entry into the model and 0.1 for retention in the model. Actual glycoprotein IIb/IIIa receptor inhibitor use and device type (Interceptor PLUS vs control), along with their interaction term, were forced into the model. A 2-sided significance level of 0.05 was used. The results are presented as the odds ratios with 95% confidence intervals. The analyses were performed using Statistical Analysis Systems, versions 8 and 9, for Windows (SAS Institute, Cary, North Carolina).
Results
The baseline patient demographics and procedural characteristics have been previously described for the AMEthyst trial. Per protocol, all patients received an EPD (Interceptor in 533, control in 264 [191 received the GuardWire and 73 received the FilterWire EZ]) and preprocedure thienopyridine therapy. Most patients were men, with a high prevalence of diabetes, hypertension, and dyslipidemia. Table 1 lists the relevant angiographic and procedural characteristics, including glycoprotein IIb/IIIa receptor inhibitor and drug-eluting stent use.
| Characteristic | Value |
|---|---|
| Interceptor PLUS assignment | 66.9% |
| Age (years) | 68.8 |
| Men | 78.9% |
| Previous stroke | 9.9% |
| Previous gastrointestinal bleed | 3.2% |
| Unstable angina pectoris | 64.1% |
| Ejection fraction <50% | 38.7% |
| Diabetes mellitus | 44.6% |
| Previous myocardial infarction | 58.8% |
| Hypertension | 86.7% |
| Smoker | 20.8% |
| Glycoprotein IIb/IIIa inhibitor use | 39.8% |
| Drug-eluting stents | 60.2% |
| Lesion length (mm) | 14.3 |
| Reference vessel diameter (mm) | 3.3 |
| Diameter stenosis (%) | 65.2 |
| Coronary narrowing classification | |
| A | 4.9% |
| B1 | 20.0% |
| B2 | 41.5% |
| C | 33.6% |
| Thrombus | 27.8% |
| Angulation >45° | 15.8% |
| Saphenous vein graft degeneration score | |
| 0 | 44.4% |
| 1 | 35.7% |
| 2 | 15.8% |
| 3 | 4.1% |
| Estimated plaque volume (mm 3 ) | 108.6 |
MACE had occurred in 7.8% of patients at 30 days (n = 58), with myocardial infarction occurring most often (55 of 58). Two patients died (0.3%) and 4 stent thromboses (0.5%) occurred. The characteristics, stratified by the presence or absence of 30-day MACE, are listed in Table 2 . Those who developed MACE were more likely to be men and to have had a longer lesion length, larger reference vessel diameter, more complex coronary narrowing classification, and higher SVG degeneration score and estimated plaque volume. The percentage of diameter stenosis was numerically greater in those who developed MACE, although this difference was not significant (p = 0.097).
| Characteristic | MACE | p Value | |
|---|---|---|---|
| No (n = 690) | Yes (n = 58) | ||
| Interceptor PLUS assignment | 66.8% | 69.0% | NS |
| Age (years) | 68.8 | 69.1 | NS |
| Men | 78.3% | 89.7% | 0.043 |
| Previous stroke | 10.4% | 7.1% | NS |
| Previous gastrointestinal bleeding | 3.4% | 1.8% | NS |
| Unstable angina pectoris | 64.1% | 65.5% | NS |
| Ejection fraction <50% | 38.2% | 43.4% | NS |
| Diabetes mellitus | 44.1% | 43.9% | NS |
| Previous myocardial infarction | 60.1% | 55.4% | NS |
| Hypertension | 86.4% | 89.7% | NS |
| Smoker | 21.3% | 15.2% | NS |
| Glycoprotein IIb/IIIa inhibitor use | 40.9% | 44.8% | NS |
| Lesion length (mm) | 13.8 | 19.1 | 0.005 |
| Reference vessel diameter (mm) | 3.2 | 3.5 | 0.003 |
| Diameter stenosis (%) | 65.1 | 68.4 | NS |
| Coronary narrowing classification | 0.005 | ||
| A | 5.3% | 0.0% | |
| B1 | 21.3% | 8.8% | |
| B2 | 41.1% | 47.4% | |
| C | 32.3% | 43.9% | |
| Thrombus | 26.6% | 35.1% | NS |
| Angulation >45° | 16.4% | 21.1% | NS |
| Saphenous vein graft degeneration score | <0.001 | ||
| 0 | 46.7% | 24.6% | |
| 1 | 34.9% | 45.6% | |
| 2 | 15.1% | 21.1% | |
| 3 | 3.3% | 8.8% | |
| Estimated plaque volume (mm 3 ) | 103.9 | 162.7 | <0.001 |
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