Jiro Aoki

Short- and Long-Term Clinical Outcome After Drug-Eluting Stent Implantation for the Percutaneous Treatment of Left Main Coronary Artery Disease Insights From the Rapamycin-Eluting and Taxus Stent Evaluated At Rotterdam Cardiology Hospital Registries (RESEARCH and T-SEARCH)

Background—The impact of drug-eluting stent (DES) implantation on the incidence of major adverse cardiovascular events in patients undergoing percutaneous intervention for left main (LM) coronary disease is largely unknown. Methods and Results—From April 2001 to December 2003, 181 patients underwent percutaneous coronary intervention for LM stenosis at our institution. The first cohort consisted of 86 patients (19 protected LM) treated with bare metal stents (pre-DES group); the second cohort comprised 95 patients (15 protected LM) treated exclusively with DES. The 2 cohorts were well balanced for all baseline characteristics. At a median follow-up of 503 days (range, 331 to 873 days), the cumulative incidence of major adverse cardiovascular events was lower in the DES cohort than in patients in the pre-DES group (24% versus 45%, respectively; hazard ratio [HR], 0.52 [95% CI, 0.31 to 0.88]; P=0.01). Total mortality did not differ between cohorts; however, there were significantly lower rates of both myocardial infarction (4% versus 12%, respectively; HR, 0.22 [95% CI, 0.07 to 0.65]; P=0.006) and target vessel revascularization (6% versus 23%, respectively; HR, 0.26 [95% CI, 0.10 to 0.65]; P=0.004) in the DES group. On multivariate analysis, use of DES, Parsonnet classification, troponin elevation at entry, distal LM location, and reference vessel diameter were independent predictors of major adverse cardiovascular events. Conclusions—When percutaneous coronary intervention is undertaken at LM lesions, routine DES implantation, which reduces the cumulative incidence of myocardial infarction and the need for target vessel revascularization compared with bare metal stents, should currently be the preferred strategy.

Incidence and clinical impact of coronary stent fracture after sirolimus-eluting stent implantation

Background: Stent fracture is one of the possible causes of restenosis after sirolimus‐eluting stents (SES) implantation. The aim of our study was to evaluate the prevalence and clinical impact of coronary stent fracture after SES implantation. Methods: From our prospective institutional database, 280 patients were treated solely with SES from August 2004 to June 2005. Among the 280 patients, 256 patients with a total of 307 lesions underwent follow‐up angiography on an average of 240 days after the procedure. Results: Stent fractures were observed in eight (2.6%) lesions. Of the eight lesions with stent fracture, five were located in the right coronary artery (RCA), two in the saphenous vein (SV) graft, and one in the left anterior descending coronary artery. The stent fractures were all in the locations that served as hinges during vessel movement in the cardiac contraction cycle. Seven of the eight stent fractures were adjacent to the edge of previously implanted or overlapped stent. Significant multivariate predictors of stent fracture were SV graft location (Odds ratio 35.88; 95% confidence interval 2.73–471.6, P = 0.006), implanted stent length (Odds ratio 1.04; 95% confidence interval 1.01–1.07, P = 0.02), and RCA location (Odds ratio 10.00; 95% confidence interval 1.11–89.67, P = 0.04). In‐stent binary restenosis rate was 37.5% and target lesion repeat revascularization rate was 50.0% in patients with stent fracture. Conclusions: Stent fracture was likely to be affected by mechanical stress provoked by rigid structures and hinge points. Stent fracture might be associated with the high incidence of target lesion revascularization.

Early stent thrombosis in patients with acute coronary syndromes treated with drug-eluting and bare metal stents: The acute catheterization and urgent intervention triage strategy trial

Background— The clinical and angiographic predictors of early (<30 days) stent thrombosis (ST) have not been reported in high-risk patients with acute coronary syndromes. Methods and Results— Qualitative and quantitative coronary angiographic analyses were performed in 3405 patients with moderate- and high-risk acute coronary syndromes in whom stents were implanted in the prospective randomized Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial, including 3043 patients (89.4%) in whom drug-eluting stents were implanted. Within 30 days, definite or probable ST occurred in 48 patients (1.4%). ST rates were not significantly different in patients treated with bare metal stents compared with drug-eluting stents (1.4% versus 1.4%; P=1.00) or with heparin plus glycoprotein IIb/IIIa inhibitors (1.1%) compared with bivalirudin with or without IIb/IIIa inhibitors (1.6% and 1.5%, respectively; P=0.26 and P=0.37, respectively). Compared with patients without ST, patients with ST more frequently had insulin-requiring diabetes mellitus and baseline renal insufficiency, a greater overall burden of coronary atherosclerosis, and suboptimal final angiographic results. ST also was more common in patients without preprocedural thienopyridine administration and with inconsistent antiplatelet drug use within 30 days. By multivariable analysis, the strongest independent predictors of definite ST were a smaller final stent minimal lumen diameter, a lack of preprocedural thienopyridine administration, the extent of coronary artery disease, and higher baseline hemoglobin level. Conclusions— Occurring in nearly 1 in 70 patients, early ST is relatively common in acute coronary syndromes, occurs with similar frequency after anticoagulation with either heparin plus glycoprotein IIb/IIIa inhibitors or bivalirudin with or without IIb/IIIa inhibitors, and is predicted by diffuse atherosclerosis, suboptimal angiographic results, and inadequate pharmacotherapy.

Role of Clopidogrel Loading Dose in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Angioplasty: Results From the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) Trial

OBJECTIVES Our aim was to determine whether a 600-mg loading dose of clopidogrel compared with 300 mg results in improved clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND A 600-mg loading dose of clopidogrel compared with 300 mg provides more rapid and potent inhibition of platelet activation. METHODS In the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, 3,602 patients with STEMI undergoing primary PCI were randomized to bivalirudin (n = 1,800) or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor (n = 1,802). Randomization was stratified by thienopyridine loading dose, which was determined before random assignment. RESULTS Patients in the 600-mg (n = 2,158) compared with the 300-mg (n = 1,153) clopidogrel loading dose group had significantly lower 30-day unadjusted rates of mortality (1.9% vs. 3.1%, p = 0.03), reinfarction (1.3% vs. 2.3%, p = 0.02), and definite or probable stent thrombosis (1.7% vs. 2.8%, p = 0.04), without higher bleeding rates. Compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin monotherapy resulted in similar reductions in net adverse cardiac event rates within the 300-mg (15.2% vs. 12.3%) and 600-mg (10.4% vs. 7.3%) clopidogrel loading dose subgroups (p(interaction) = 0.41). By multivariable analysis, a 600-mg clopidogrel loading dose was an independent predictor of lower rates of 30-day major adverse cardiac events (hazard ratio: 0.72 [95% confidence interval: 0.53 to 0.98], p = 0.04). CONCLUSIONS In patients with STEMI undergoing primary PCI with contemporary anticoagulation regimens, a 600-mg loading dose of clopidogrel may safely reduce 30-day ischemic adverse event rates compared with a 300-mg loading dose. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966).

5-year clinical outcomes after sirolimus-eluting stent implantation insights from a patient-level pooled analysis of 4 randomized trials comparing sirolimus-eluting stents with bare-metal stents.

OBJECTIVES Five-year clinical follow-up has been scheduled per protocol by the 4 Cypher (Cordis/Johnson & Johnson, Warren, New Jersey) sirolimus-eluting stent (SES) versus bare-metal stent (BMS) randomized trials. BACKGROUND A delayed arterial healing response after drug-eluting stent implantation has raised concerns about the long-term safety of drug-eluting stents. METHODS In a pooled analysis of 4 randomized trials, 1,748 patients were assigned to receive either an SES (n = 878) or BMS (n = 870). RESULTS At 5 years, there was no significant difference in the rate of death, myocardial infarction (MI), or the composite of death/MI between the 2 groups (15.1% in the SES group vs. 13.6% in the BMS group; p = 0.36). The 5-year incidence of stent thrombosis by the Academic Research Consortium definition did not differ between SES and BMS (definite/probable stent thrombosis, 2.1% vs. 2.0%; p = 0.99). The incidence of very late stent thrombosis was also similar between the SES and BMS groups (1.4% vs. 0.7%; p = 0.22). The annualized rates of definite/probable stent thrombosis after 1 year were 0.4% for SES and 0.2% for BMS. The 5-year incidence of target vessel revascularization was significantly lower in the SES group (15.2% vs. 30.1%; p < 0.0001). CONCLUSIONS In this patient-level pooled analysis, overall use of SES compared with BMS demonstrated persistent superior efficacy at 5 years in terms of a reduction in target vessel revascularization, without an increase in rates of death, MI, or stent thrombosis. (The Initial Double-Blind Drug-Eluting Stent vs Bare-Metal Stent Study, NCT00233805; The Study of the BX Velocity Stent in the Treatment of De Novo Artery Lesions, NCT00381420; Study of Sirolimus-Coated BX VELOCITY Balloon-Expandable Stent in Treatment of de Novo Native Coronary Artery Lesions [SIRIUS], NCT00232765; The Study of the BX VELOCITY Stent In Patients With De Novo Coronary Artery Lesions, NCT00235144).

Coronary artery remodelling is related to plaque composition

Objective: To assess the potential relation between plaque composition and vascular remodelling by using spectral analysis of intravascular ultrasound (IVUS) radiofrequency data. Methods and results: 41 coronary vessels with non-significant (< 50% diameter stenosis by angiography), ⩽ 20 mm, non-ostial lesions located in non-culprit vessels underwent IVUS interrogation. IVUS radiofrequency data obtained with a 30 MHz catheter, were analysed with IVUS virtual histology software. A remodelling index (RI) was calculated and divided into three groups. Lesions with RI ⩾ 1.05 were considered to have positive remodelling and lesions with RI ⩽ 0.95 were considered to have negative remodelling. Lesions with RI ⩾ 1.05 had a significantly larger lipid core than lesions with RI 0.96–1.04 and RI ⩽ 0.95 (22.1 (6.3) v 15.1 (7.6) v 6.6 (6.9), p < 0.0001). A positive correlation between lipid core and RI (r  =  0.83, p < 0.0001) and an inverse correlation between fibrous tissue and RI (r  =  −0.45, p  =  0.003) were also significant. All of the positively remodelled lesions were thin cap fibroatheroma or fibroatheromatous lesions, whereas negatively remodelled lesions had a more stable phenotype, with 64% having pathological intimal thickening, 29% being fibrocalcific lesions, and only 7% fibroatheromatous lesions (p < 0.0001). Conclusions: In this study, in vivo plaque composition and morphology assessed by spectral analysis of IVUS radiofrequency data were related to coronary artery remodelling.

Coronary Artery Aneurysms After Drug-Eluting Stent Implantation

Drug-eluting stents (DES), which locally elute antiproliferative drugs, can dramatically inhibit neointimal growth. However, several pathological studies have indicated that DES may delay healing after vascular injury, and DES implantation may be theoretically associated with a risk of coronary artery aneurysm formation. Coronary aneurysms have been reported from 3 days to up to 4 years after DES implantation procedures, with varying clinical presentations. The incidence of coronary artery aneurysms after DES implantation is low within the first 9 months, with a reported incidence of 0.2% to 2.3%, a rate similar to that reported after bare-metal stent (BMS) implantation (0.3% to 3.9%) in the DES versus BMS randomized trials. However, the true incidence of coronary aneurysms in an unselected patient population is still largely unknown. This article reviews the published literature on coronary artery aneurysms specifically relating to DES.

Peristent Remodeling and Neointimal Suppression 2 Years After Polymer-Based, Paclitaxel-Eluting Stent Implantation: Insights From Serial Intravascular Ultrasound Analysis in the TAXUS II Study

Background— The purpose of this study was to evaluate long-term vascular responses as long as 2 years after implantation of polymer-based, paclitaxel-eluting stents in contrast to uncoated stents. Methods and Results— TAXUS II is a randomized, double-blind trial comparing slow-release (SR) and moderate-release (MR) TAXUS stents with bare-metal control stents (BMSs). One hundred sixty-one event-free patients (SR, 43; MR, 41; and BMS, 77) underwent serial intravascular ultrasound (IVUS) analysis after the procedure and at 6 months and 2 years. At 2 years, neointimal responses continued to be significantly suppressed in the SR and MR groups when compared with the BMS group (BMS, 1.49±1.12 mm2; SR, 0.94±0.76 mm2 [P=0.004]; and MR, 1.06±0.90 mm2 [P=0.02]). Between 6 months and 2 years, the BMS group showed compaction of the neointima (&Dgr;, −0.22±1.05 mm2 [P=0.08]). In contrast, both the SR and MR groups exhibited an increase (&Dgr; SR, 0.30±0.76 mm2 (P=0.01); MR, 0.41±0.94 mm2 [P=0.009]). Between 6 months and 2 years, the initial increase in plaque outside the stent regressed in the BMS and SR groups to levels comparable to those after the procedure, whereas expansive remodeling partially regressed in the MR group (&Dgr; between after the procedure and 2 years BMS, −0.34±1.28 mm2 [P=0.05]; SR, −0.02±1.40 mm2 [P=0.93]; MR, 0.32±1.56 mm2 [P=0.27]). Conclusions— The 2-year follow-up demonstrates that neointimal suppression was dose independent and that this effect was still sustained at 2 years. However, the increase in area outside the stent seen at 6 months regressed to different extents in a dose-dependent manner at 2 years.

Classification and Potential Mechanisms of Intravascular Ultrasound Patterns of Stent Fracture

We sought to examine the intravascular ultrasound (IVUS) findings of stent fracture. Stent fracture has been implicated as a cause of drug-eluting stent failure. IVUS is more likely to identify mechanisms of stent failure -- including stent fracture -- than angiography. Twenty stent fractures diagnosed by IVUS in 17 patients were evaluated. Eighteen stent fractures (90%) occurred in sirolimus-eluting Cypher stents, and 2 stent fractures (10%) occurred in bare metal stents, but none occurred in paclitaxel-eluting Taxus stents. Half of the stent fractures presented < or =1 year after implantation, and (1/2) presented >1 year after implantation. IVUS analysis showed that 9 stent fractures were complete (45%) and 11 were partial (55%); 10 (50%) were adjacent to stent metal overlap; and 5 occurred in a coronary aneurysm accompanied by malapposition (all Cypher stents) despite the absence of an aneurysm at index stenting. Compared with 60 matched control segments in patients without stent fracture, but with similar clinical events, the stent fracture group had longer stent segments (45.2 +/- 23.0 vs 28.5 +/- 14.9 mm, p = 0.003). Comparing stent fractures associated with an aneurysm (n = 5) with those that did not occur in association with an aneurysm (n = 15) showed that complete stent fracture was more frequent (100% vs 27%, p = 0.008), and all presented >1 year after index stenting (vs 33%, p = 0.03). In conclusion, IVUS is helpful to identify stent fracture as a cause of stent failure and to understand possible mechanisms of stent fracture such as aneurysm formation.

Effectiveness of Drug-Eluting Stent Implantation for Patients With Unprotected Left Main Coronary Artery Stenosis

This study was aimed to evaluate outcomes of patients with unprotected left main coronary artery (LMCA) stenosis who were treated with drug-eluting stents. Sixty-three consecutive patients with unprotected LMCA stenosis were treated with sirolimus-eluting stents in 52 (83%) patients and paclitaxel-eluting stents in 11 (17%) patients, in whom percutaneous intervention was considered the sole alternative because of high surgical risk and/or patient preference. Urgent percutaneous coronary intervention within 24 hours after angiography was performed in 6 (10%) patients. The patients were predominantly at high surgical risk with 35 (56%) having EuroSCORE >6 and 39 (62%) having Parsonnet score >15. Involvement of the distal LMCA was observed in 46 (73%) patients. Procedural success was achieved in all patients. Intravascular ultrasound was used in 51 (81%) patients. Single-stenting strategy was adopted in 36 (78%) patients with bifurcation stenosis. There were no death, Q-wave myocardial infarction, stent thrombosis, or urgent repeat revascularization events during hospitalization. Over a mean follow-up of 11.7 +/- 7.7 months, 18 (29%) patients experienced major adverse cardiac events, including 3 (5%) deaths, 7 (11%) myocardial infarctions, and 10 (16%) target lesion revascularizations. Stent thrombosis developed in 1 (0.6%) patient at 35 days after the procedure. Bifurcation involvement was an independent predictor of major adverse cardiac events by multivariate analysis (hazard ratio 12.90, 95% confidence interval 1.36 to 122.45, p = 0.0259). In conclusion, drug-eluting stent placement for unprotected LMCA stenosis may be a feasible therapeutic alternative in patients at high surgical risk. However, bifurcation stenosis remains a significant predictor of unfavorable clinical outcome.