Compared to paclitaxel-eluting stents (PESs) and sirolimus-eluting stents (SESs), a paucity of data exists regarding the clinical outcome of everolimus-eluting stents (EESs) in unselected patients with the entire spectrum of obstructive coronary artery disease. The present study cohort included 6,615 consecutive patients at Washington Hospital Center who underwent coronary artery stent implantation with EESs (n = 519), PESs (n = 2,036), or SESs (n = 4,060). Patients who received bare metal stents, zotarolimus-eluting stents, or 2 different drug-eluting stent types were excluded. The analyzed clinical end points were death, death or Q-wave myocardial infarction, target lesion revascularization (TLR), target vessel revascularization, definite stent thrombosis, and major adverse cardiac events, defined as the composite of death, Q-wave myocardial infarction, or TLR at 1 year. The groups were well matched for the conventional risk factors for coronary artery disease, except for systemic hypertension, which differed among the groups. The unadjusted end points for EESs and PESs were death (4.5% vs 7.1%; p = 0.03), TLR (3.4% vs 4.6%; p = 0.24), target vessel revascularization (5.6% vs 7.1%; p = 0.46), death or Q-wave myocardial infarction (4.5% vs 7.4%; p = 0.02), and definite stent thrombosis (0.0% vs 0.7%; p = 0.09). The unadjusted end points for EES and SES were death (4.5% vs 5.2%; p = 0.45), TLR (3.4% vs 5.8%; p = 0.3), target vessel revascularization (5.6% vs 8.6%; p = 0.05), death or Q-wave myocardial infarction (4.5% vs 5.4%; p = 0.39), and definite stent thrombosis (0.0% vs 1.08%; p = 0.003). The rates of major adverse cardiac events were similar among the 3 groups. After multivariate analysis, the rate of death or Q-wave myocardial infarction between the EES and PES groups was no longer significant (hazard ratio 1.14, 95% confidence interval 0.59 to 2.20, p = 0.70). In conclusion, the results of the present study suggest the use of EES in routine clinical practice is both safe and effective but offers no clinically relevant advantage in terms of hard end points compared to PES or SES.
Compared to bare metal stents, the first-generation drug-eluting stents, sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs), have been shown to reduce the rates of restenosis and target vessel revascularization (TVR) in patients undergoing percutaneous coronary intervention. The everolimus-eluting stents (EESs), XIENCE V (Abbott Vascular Devices, Redwood City, California) and PROMUS (Boston Scientific, Natick, Massachusetts), were designed to provide superior long-term safety with similar or greater efficacy compared to the first-generation drug-eluting stents. Everolimus, a rapamycin derivative that inhibits growth factor-stimulated cellular proliferation, has been mounted on a nonadhesive, durable, biocompatible fluoropolymer using a flexible and highly deliverable cobalt chromium stent. The drug load is 100 μg/cm 2 for all stent sizes. Everolimus is released in a controlled fashion, with 80% of the drug eluted within 1 month and the remainder within 4 months. Most clinical trials comparing the XIENCE V/PROMUS stent with the first-generation drug-eluting stents have included low-risk, stable patients with noncomplex lesions. The aim of the present study was therefore to establish the safety and effectiveness of EESs compared to both PESs and SESs in an unselected, consecutive, patient cohort.
Methods
The present single-center, retrospective study included 6,615 consecutive patients who had undergone coronary artery stent implantation with EESs (n = 519), PESs (n = 2,036), or SESs (n = 4,060) at Washington Hospital Center from 2003 to 2009. The patients who had received bare metal stents, zotarolimus-eluting stents, or 2 different drug-eluting stent types were excluded. All patients provided written informed consent. The study complied with the Declaration of Helsinki for investigation in humans and was approved by the institutional ethics committee of Washington Hospital Center. The procedures were performed according to standard clinical guidelines. In all cases, the interventional strategy and the use of adjunctive devices and pharmacotherapy was at the discretion of the operating interventional cardiologist. All patients received aspirin 325 mg before the procedure and were recommended to continue this regimen indefinitely. In addition, clopidogrel 75 mg/day after a 300- or 600-mg loading dose was begun before the procedure and continued for 12 months. The follow-up data at 30 days and 6 and 12 months were obtained by telephone interview, mailed questionnaire, or outpatient review.
The analyzed clinical parameters were death, death or Q-wave myocardial infarction, target lesion revascularization (TLR), TVR, definite stent thrombosis, and major adverse cardiac events, defined as the composite of death, Q-wave myocardial infarction, or TLR at 1 year. Q-wave myocardial infarction was defined as evidence of new Q waves on the electrocardiogram at myocardial infarction. Myocardial infarction was defined as a total creatinine kinase increase ≥2× the upper limit of normal and/or creatinine kinase (MB fraction) ≥20 ng/ml, together with symptoms and/or ischemic electrocardiographic changes. Hypercholesterolemia was defined as fasting cholesterol >250 mg/dl or the use of lipid-lowering therapy. Systemic hypertension was defined as blood pressure >140/90 mm Hg or the use of antihypertensive therapy. Renal impairment was defined as serum creatinine >1.2 mg/dl. Congestive heart failure was defined as evidence of fluid retention from cardiac causes before admission. Angiographic success was defined as postprocedural stenosis of ≤30% and Thrombolysis In Myocardial Infarction flow grade 3. Gastrointestinal bleeding was defined as evidence of upper (coffee-ground emesis, endoscopy demonstrating active bleeding) or lower (melena, hematochezia, or endoscopy demonstrating an active bleeding site) gastrointestinal bleeding. TLR was defined as ischemia-driven percutaneous or surgical repeat intervention in the stent or within 5 mm proximal or distal to the stent. Stent thrombosis was defined in accordance with the Academic Research Consortium definitions as definite, probable, or possible.
Statistical analysis was performed using SAS, version 8.2 (SAS Institute, Cary, North Carolina). Continuous variables and categorical variables are expressed as the mean ± SD and percentages, respectively. Analyses of difference among the 3 drug-eluting stents were performed using analysis of variance for continuous variables and the chi-square test or Fisher’s exact test for categorical variables. After univariate analysis for baseline clinical and procedural characteristics, the following characteristics with p <0.1 were incorporated into the multivariate analysis: age, male gender, presentation with acute myocardial infarction, presentation with cardiogenic shock, known history of systemic hypertension, diabetes mellitus, chronic renal impairment, family history of coronary artery disease or heart failure, history of coronary artery disease, myocardial infarction, or coronary revascularization, body mass index, number of diseased vessels, use of intra-aortic balloon pump, intravascular ultrasonography, glycoprotein IIb/IIIa inhibitor or bivalirudin, major bleeding complications, gastrointestinal bleeding, type C lesion, and number and length of implanted drug-eluting stents. For variables with a 3-group p value <0.05, 2 subsequent pair wise comparisons for EES versus PES and EES versus SES were performed with Bonferroni’s correction for p value significance (p <0.025). Survival analysis was done using the Kaplan-Meier method, and differences in the survival parameters were assessed using the log-rank test. p Values <0.05 were considered statistically significant.
Results
The baseline characteristics of the patients are summarized in Table 1 . The 3 cohorts were well matched for the conventional risk factors for coronary artery disease, except for systemic hypertension, which differed. The 3 cohorts also differed with respect to the body mass index, history of myocardial infarction, surgical revascularization, and renal impairment. The angiographic and procedural characteristics are summarized in Table 2 . The 3 cohorts differed in the location of the target lesion, the American College of Cardiology/American Heart Association lesion type, and the number and length of drug-eluting stents. The use of glycoprotein IIb/IIIa inhibitors, bivalirudin, and intravascular ultrasonography also differed, which might have been a reflection of the relatively recent adoption of such adjunctive agents in routine clinical practice.
| Characteristic | EES Group (n = 519) | PES Group (n = 2,036) | SES Group (n = 4,059) | p Value |
|---|---|---|---|---|
| Men | 349 (67.2%) | 1,348 (66.2%) | 2,605 (64.2%) | 0.16 |
| Age (years) | 64.6 ± 10.7 | 65.3 ± 12.2 | 64.9 ± 11.7 | 0.23 |
| Systemic hypertension ⁎ | 458 (88.2%) | 1,712 (84.1%) | 3,369 (83%) | 0.01 |
| Diabetes mellitus | 197 (37.9%) | 709 (34.8%) | 1,413 (34.8%) | 0.37 |
| Hypercholesterolemia † | 469 (90.5%) | 1,767 (86.8%) | 3,560 (87.7%) | 0.07 |
| Smoker | 99 (19.1%) | 393 (19.3%) | 767 (18.9%) | 1.0 |
| Acute myocardial infarction | 47 (9.1%) | 236 (11.6%) | 503 (12.4%) | 0.8 |
| Cardiogenic shock | 9 (1.7%) | 53 (2.6%) | 114 (2.8%) | 0.32 |
| Body mass index (kg/m 2 ) | 30.6 ± 6.3 | 29.2 ± 5.9 | 29.6 ± 6.4 | <0.001 |
| History of | ||||
| Myocardial infarction | 145 (28%) | 483 (23.7%) | 852 (21%) | <0.001 |
| Percutaneous coronary intervention | 151 (29%) | 570 (28%) | 1,068 (26.3%) | 0.23 |
| Coronary artery bypass surgery | 127 (24.5%) | 405 (19.9%) | 735 (18.1%) | 0.001 |
| Renal impairment | 42 (8%) | 291 (14.3%) | 491 (12.1%) | <0.001 |
| Congestive heart failure | 68 (13.1%) | 261 (12.8%) | 593 (14.6%) | 0.16 |
⁎ History of hypertension diagnosed and/or treated with medication or currently treated with diet and/or medication by a physician.
† Included patients with previously documented diagnosis of hypercholesterolemia be treated with diet or medication or new diagnosis made during this hospitalization with elevated total cholesterol >160 mg/dl; did not include elevated triglycerides.
| Variable | EES Group | PES Group | SES Group | p value |
|---|---|---|---|---|
| Angiographic | ||||
| Patients (n) | 808 | 3,542 | 7,385 | |
| Target coronary lesion location | <0.001 | |||
| Right coronary | 201 (24.9%) | 1,206 (34%) | 2,196 (29.7%) | |
| Left main stem | 26 (3.2%) | 59 (1.7%) | 144 (1.9%) | |
| Left anterior descending | 330 (40.9%) | 1,249 (35.3%) | 2,929 (39.7%) | |
| Left circumflex | 210 (26.1%) | 827 (23.3%) | 210 (23.2%) | |
| Saphenous vein graft | 37 (4.6%) | 180 (5.1%) | 369 (5%) | |
| American college of Cardiology/American Heart Association lesion type | <0.001 | |||
| A | 104 (13.1%) | 178 (5.2%) | 496 (7.1%) | |
| B1, B2 | 322 (40.5%) | 2,409 (70.9%) | 5,132 (72.9%) | |
| C | 369 (46.4%) | 809 (23.8%) | 1,407 (20%) | |
| Angiographic success | 777 (96.7%) | 3,425 (98.2%) | 7,193 (98%) | 0.13 |
| No reflow | 2 (0.2%) | 16 (0.5%) | 26 (0.4%) | 0.5 |
| Intravascular ultrasonography | 432 (53.5%) | 2,151 (62.7%) | 4,729 (65.5%) | <0.001 |
| Procedural | ||||
| Patients (n) | 519 | 2,036 | 4,059 | |
| Drug-eluting stents | ||||
| Number implanted | 1.5 ± 0.8 | 1.5 ± 0.77 | 1.5 ± 0.75 | 0.001 |
| Average length (mm) | 18.1 ± 5.5 | 19.5 ± 6.4 | 20.8 ± 6.7 | <0.001 |
| Average diameter (mm) | 3.3 ± 1.0 | 3.1 ± 1.4 | 3.1 ± 2.3 | 0.31 |
| Glycoprotein IIb/IIIa inhibitor | 23 (4.5%) | 173 (8.5%) | 491 (12.1%) | <0.001 |
| Bivalirudin | 452 (87.1%) | 1,598 (78.5%) | 2,890 (71.2%) | <0.001 |
The in-hospital complications are summarized in Table 3 . The 3 cohorts did not differ in any of the examined parameters. The in-hospital rate of death, Q-wave myocardial infarction, coronary artery bypass surgery, and cerebrovascular events was 1.5%, 0.4%, 0.3%, and 0.4%, respectively. At 12 months, clinical follow-up was available for 99.6% of the EES group, 99.8% of the PES group, and 99.7% of the SES group. The unadjusted outcomes for the 3 cohorts are summarized in Table 4 . At 30 days’ follow-up, no differences were found in any of the analyzed clinical end points. At 6 months, the 3 groups differed in the unadjusted rates of death (p = 0.05), TLR (p = 0.04), TVR (p = 0.002), death or Q-wave myocardial infarction (p = 0.04), major adverse cardiac events (p = 0.02) and definite stent thrombosis (p = 0.05). At 12 months’ follow-up, the unadjusted rates of death (p = 0.005), TLR (p = 0.02), TVR (p = 0.02), death or Q-wave myocardial infarction (p = 0.003), and definite stent thrombosis (p = 0.02) remained significant.
| Complication | EES Group (n = 519) | PES Group (n = 2,036) | SES Group (n = 4,059) | p Value |
|---|---|---|---|---|
| Death | 9 (1.7%) | 2 9 (1.4%) | 53 (1.3%) | 0.66 |
| Q-wave myocardial infarction | 1 (0.2%) | 12 (0.6%) | 16 (0.4%) | 0.32 |
| Coronary artery bypass graft | 2 (0.4%) | 6 (0.3%) | 4 (0.1%) | 0.28 |
| Cerebrovascular event | 3 (0.6%) | 6 (0.3%) | 16 (0.4%) | 0.63 |
| Major bleeding | 5 (1.0%) | 43 (2.1%) | 57 (1.4%) | 0.08 |
| Gastrointestinal bleeding | 0 | 12 (0.6%) | 24 (0.6%) | 0.21 |
| Variable | EES Group (%) | PES Group (%) | SES Group (%) | p Value |
|---|---|---|---|---|
| 30 Days | ||||
| Death | 1.7 | 2.3 | 1.7 | 0.31 |
| Target lesion revascularization | 0.0 | 1.0 | 0.8 | 0.07 |
| Target vessel revascularization | 0.2 | 1.4 | 1.3 | 0.07 |
| Death or Q-wave myocardial infarction | 1.5 | 2.2 | 1.7 | 0.36 |
| Major adverse cardiac events | 1.5 | 3.1 | 2.4 | 0.08 |
| Definite stent thrombosis | 0.0 | 0.6 | 0.8 | 0.09 |
| 6 Months | ||||
| Death | 3.5 | 4.9 | 3.6 | 0.05 |
| Target lesion revascularization | 0.8 | 3.0 | 3.5 | 0.04 |
| Target vessel revascularization | 1.8 | 4.2 | 5.1 | 0.002 |
| Death or Q-wave myocardial infarction | 3.5 | 5.1 | 3.8 | 0.04 |
| Major adverse cardiac events | 4.2 | 7.7 | 7.0 | 0.02 |
| Definite stent thrombosis | 0.0 | 0.7 | 1.0 | 0.05 |
| 12 Months | ||||
| Death | 4.5 | 7.1 | 5.2 | 0.005 |
| Target lesion revascularization | 3.4 | 4.6 | 5.8 | 0.02 |
| Target vessel revascularization | 5.6 | 7.1 | 8.6 | 0.02 |
| Death or Q-wave myocardial infarction | 4.5 | 7.4 | 5.4 | 0.003 |
| Major adverse cardiac events | 7.7 | 11.4 | 10.6 | 0.06 |
| Definite stent thrombosis | 0.0 | 0.7 | 1.1 | 0.02 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
