Ken Kozuma

A randomized trial evaluating everolimus-eluting Absorb bioresorbable scaffolds vs. everolimus-eluting metallic stents in patients with coronary artery disease: ABSORB Japan

AIMS Theoretically, bioresorbable vascular scaffolds (BVSs) may provide superior long-term results compared with permanent metallic drug-eluting stents (DESs). However, whether BVSs are as safe and effective as metallic DESs prior to complete bioresorption is unknown. METHODS AND RESULTS ABSORB Japan was a single-blind, multicentre, active-controlled, randomized trial designed to support regulatory approval of the Absorb BVS in Japan. Eligible patients with one or two de novo lesions in different epicardial vessels were randomized at 38 Japanese sites in a 2:1 ratio to Absorb BVS vs. cobalt-chromium everolimus-eluting stents (CoCr-EESs). The primary endpoint was target lesion failure [TLF: a composite of cardiac death, myocardial infarction attributable to target vessel, or ischaemia-driven target lesion revascularization (ID-TLR)] at 12 months, powered for non-inferiority. The major secondary endpoint was angiographic in-segment late lumen loss (LLL) at 13 months. A total of 400 patients were randomized to BVSs (266 patients and 275 lesions) or CoCr-EESs (134 patients and 137 lesions). TLF through 12 months was 4.2% with BVSs and 3.8% with CoCr-EESs [difference (upper one-sided 95% confidence limit) = 0.39% (3.95%); Pnon-inferiority < 0.0001]. Definite/probable stent/scaffold thrombosis at 12 months occurred in 1.5% of the patients with both devices (P = 1.0), and ID-TLR for restenosis was infrequent (1.1% with BVSs and 1.5% with CoCr-EESs, P = 1.0). With 96.0% angiographic follow-up, in-segment LLL at 13 months was 0.13 ± 0.30 mm with BVSs and 0.12 ± 0.32 mm with CoCr-EESs [difference (upper one-sided 95% confidence limit) = 0.01 (0.07); Pnon-inferiority < 0.0001). CONCLUSION In the ABSORB Japan randomized trial, 12-month clinical and 13-month angiographic outcomes of BVSs were comparable to CoCr-EESs. CLINICAL REGISTRATION ClinicalTrials.gov, number NCT01844284.

Comparisons of Baseline Demographics, Clinical Presentation, and Long-Term Outcome Among Patients With Early, Late, and Very Late Stent Thrombosis of Sirolimus-Eluting Stents Observations From the Registry of Stent Thrombosis for Review and Reevaluation (RESTART)

Background— Stent thrombosis (ST) after sirolimus-eluting stent implantation has not yet been adequately characterized, mainly because of its low incidence. Methods and Results— The Registry of Stent Thrombosis for Review and Reevaluation (RESTART) is a Japanese nationwide registry of sirolimus-eluting stent–associated ST comprising 611 patients with definite ST (early [within 30 days; EST], 322 patients; late [between 31 and 365 days; LST], 105 patients; and very late [>1 year; VLST], 184 patients). Baseline demographics, clinical presentation, and long-term outcome of sirolimus-eluting stent–associated ST were compared among patients with EST, LST, and VLST. Baseline demographics were significantly different according to the timing of ST. Characteristic demographic factors for LST/VLST versus EST identified by multivariable model were hemodialysis, end-stage renal disease not on hemodialysis, absence of circumflex target, target of chronic total occlusion, prior percutaneous coronary intervention, and age <65 years. For LST versus VLST, they were hemodialysis, heart failure, insulin-dependent diabetes mellitus, and low body mass index. Patients with LST had a significantly higher rate of Thrombolysis in Myocardial Infarction grade 2/3 flow (36%) at the time of ST than those with EST (13%) (P<0.0001) and VLST (17%; P<0.0001). Mortality rate at 1 year after ST was significantly lower in patients with VLST (10.5%) compared with those with EST (22.4%; P=0.003) or LST (23.5%; P=0.009). Conclusion— ST timing–dependent differences in baseline demographic features, Thrombolysis in Myocardial Infarction flow grade, and mortality rate suggest possible differences in the predominant pathophysiological mechanisms of ST according to timing after sirolimus-eluting stent implantation.

Biodegradable Polymer Biolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent : A Randomized, Controlled, Noninferiority Trial

OBJECTIVES NEXT (NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial) was designed for evaluating the noninferiority of a biolimus-eluting stent (BES) relative to an everolimus-eluting stent (EES) in terms of target lesion revascularization (TLR) at 1 year. BACKGROUND Efficacy and safety data comparing biodegradable polymer BES with durable polymer cobalt-chromium EES are currently limited. METHODS The NEXT trial is a prospective, multicenter, randomized, open-label, noninferiority trial comparing BES with EES. Between May and October 2011, 3,235 patients were randomly assigned to receive either BES (n = 1,617) or EES (n = 1,618). RESULTS At 1 year, the primary efficacy endpoint of TLR occurred in 67 patients (4.2%) in the BES group, and in 66 patients (4.2%) in the EES group, demonstrating noninferiority of BES relative to EES (p for noninferiority <0.0001, and p for superiority = 0.93). Cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (0.25% vs. 0.06%, p = 0.18). An angiographic substudy enrolling 528 patients (BES: n = 263, and EES: n = 265) demonstrated noninferiority of BES relative to EES regarding the primary angiographic endpoint of in-segment late loss (0.03 ± 0.39 mm vs. 0.06 ± 0.45 mm, p for noninferiority <0.0001, and p for superiority = 0.52) at 266 ± 43 days after stent implantation. CONCLUSIONS One-year clinical and angiographic outcome after BES implantation was noninferior to and not different from that after EES implantation in a mostly stable coronary artery disease population. One-year clinical outcome after both BES and EES use was excellent, with a low rate of TLR and extremely low rate of stent thrombosis.

OCT Compared With IVUS in a Coronary Lesion Assessment The OPUS-CLASS Study

OBJECTIVES The aim of this study was to investigate the reliability of frequency domain optical coherence tomography (FD-OCT) for coronary measurements compared with quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). BACKGROUND Accurate luminal measurement is expected in FD-OCT because this technology offers high resolution and excellent contrast between lumen and vessel wall. METHODS In 5 medical centers, 100 patients with coronary artery disease were prospectively studied by using angiography, FD-OCT, and IVUS. In addition, 5 phantom models of known lumen dimensions (lumen diameter 3.08 mm; lumen area 7.45 mm(2)) were examined using FD-OCT and IVUS. Quantitative image analyses of the coronary arteries and phantom models were performed by an independent core laboratory. RESULTS In the clinical study, the mean minimum lumen diameter measured by QCA was significantly smaller than that measured by FD-OCT (1.81 ± 0.72 mm vs. 1.91 ± 0.69 mm; p < 0.001) and the minimum lumen diameter measured by IVUS was significantly greater than that measured by FD-OCT (2.09 ± 0.60 mm vs. 1.91 ± 0.69 mm; p < 0.001). The minimum lumen area measured by IVUS was significantly greater than that by FD-OCT (3.68 ± 2.06 mm(2) vs. 3.27 ± 2.22 mm(2); p < 0.001), although a significant correlation was observed between the 2 imaging techniques (r = 0.95, p < 0.001; mean difference 0.41 mm(2)). Both FD-OCT and IVUS exhibited good interobserver reproducibility, but the root-mean-squared deviation between measurements was approximately twice as high for the IVUS measurements compared with the FD-OCT measurements (0.32 mm(2) vs. 0.16 mm(2)). In a phantom model, the mean lumen area according to FD-OCT was equal to the actual lumen area of the phantom model, with low SD; IVUS overestimated the lumen area and was less reproducible than FD-OCT (8.03 ± 0.58 mm(2) vs. 7.45 ± 0.17 mm(2); p < 0.001). CONCLUSIONS The results of this prospective multicenter study demonstrate that FD-OCT provides accurate and reproducible quantitative measurements of coronary dimensions in the clinical setting.

Upfront thrombus aspiration in primary coronary intervention for patients with ST-segment elevation acute myocardial infarction: report of the VAMPIRE (VAcuuM asPIration thrombus REmoval) trial.

OBJECTIVES This study evaluated safety and efficacy of upfront thrombus aspiration during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND Distal embolization during primary PCI results in reduced myocardial perfusion and poor clinical outcomes. METHODS The VAMPIRE (VAcuuM asPIration thrombus REmoval) study was a prospective, randomized, controlled multicenter trial conducted in 23 institutions. Patients (N = 355) presenting within 24 h of STEMI symptoms onset were randomized to primary PCI with (n = 180) or without (n = 175) upfront thrombus aspiration using Nipros TransVascular Aspiration Catheter (Osaka, Japan). RESULTS The TransVascular Aspiration Catheter reached the lesion in 100% of cases. It successfully crossed the target obstruction in 86% without any delay in procedure time or time to reperfusion; whereas macroscopic thrombi were removed in 75% of the cases. Procedure success was similar between groups (98.9% vs. 98.3%). There was a trend toward lower incidence of slow or no reflow (primary end point-defined as a Thrombolysis In Myocardial Infarction flow grade <3) in patients treated with aspiration versus conventional primary PCI (12.4% vs. 19.4%, p = 0.07). Rate of myocardial blush grade 3 was higher in the aspiration group (46.0% vs. 20.5%, p < 0.001). Aspiration was most effective in patients presenting after 6 h of symptoms onset (slow flow rate: 8.1% vs. 37.6%, p = 0.01). CONCLUSIONS This study suggested the safety of primary PCI with upfront thrombectomy using a novel device in patients with STEMI. The study showed a trend toward improved myocardial perfusion and lower clinical events in patients treated with aspiration. Patients presenting late after STEMI appear to benefit the most from thrombectomy.

Comparison of Everolimus-Eluting and Sirolimus-Eluting Coronary Stents 1-Year Outcomes from the Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial (RESET)

Background— Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar outcomes. However, only 1 trial was powered for a clinical end point, and no trial was powered for evaluating target-lesion revascularization. Methods and Results— Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. The trial was powered for evaluating noninferiority of EES relative to SES in terms of target-lesion revascularization. From February and July 2010, 3197 patients were randomly assigned to receive either EES (1597 patients) or SES (1600 patients). At 1 year, the primary efficacy end point of target-lesion revascularization occurred in 65 patients (4.3%) in the EES group and in 76 patients (5.0%) in the SES group, demonstrating noninferiority of EES to SES ( P noninferiority<0.0001, and P superiority=0.34). Cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (0.32% versus 0.38%, P =0.77). An angiographic substudy enrolling 571 patients (EES, 285 patients and SES, 286 patients) demonstrated noninferiority of EES relative to SES regarding the primary angiographic end point of in-segment late loss (0.06±0.37 mm versus 0.02±0.46 mm, P noninferiority<0.0001, and P superiority=0.24) at 278±63 days after index stent implantation. Conclusions— One-year clinical and angiographic outcome after EES implantation was noninferior to and not different from that after SES implantation in a stable coronary artery disease population with relatively less complex coronary anatomy. One-year clinical outcome after both EES and SES use was excellent with a low rate of target-lesion revascularization and a very low rate of stent thrombosis. Clinical Trial Registration— URL: . Unique identifier: [NCT01035450][1]. # Clinical Perspective {#article-title-27} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01035450&atom=%2Fcirculationaha%2F126%2F10%2F1225.atomBackground— Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar outcomes. However, only 1 trial was powered for a clinical end point, and no trial was powered for evaluating target-lesion revascularization. Methods and Results— Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. The trial was powered for evaluating noninferiority of EES relative to SES in terms of target-lesion revascularization. From February and July 2010, 3197 patients were randomly assigned to receive either EES (1597 patients) or SES (1600 patients). At 1 year, the primary efficacy end point of target-lesion revascularization occurred in 65 patients (4.3%) in the EES group and in 76 patients (5.0%) in the SES group, demonstrating noninferiority of EES to SES (Pnoninferiority<0.0001, and Psuperiority=0.34). Cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (0.32% versus 0.38%, P=0.77). An angiographic substudy enrolling 571 patients (EES, 285 patients and SES, 286 patients) demonstrated noninferiority of EES relative to SES regarding the primary angiographic end point of in-segment late loss (0.06±0.37 mm versus 0.02±0.46 mm, Pnoninferiority<0.0001, and Psuperiority=0.24) at 278±63 days after index stent implantation. Conclusions— One-year clinical and angiographic outcome after EES implantation was noninferior to and not different from that after SES implantation in a stable coronary artery disease population with relatively less complex coronary anatomy. One-year clinical outcome after both EES and SES use was excellent with a low rate of target-lesion revascularization and a very low rate of stent thrombosis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035450.

Incidence, Risk Factors, and Clinical Sequelae of Angiographic Peri-Stent Contrast Staining After Sirolimus-Eluting Stent Implantation

Background— We have noted abnormal angiographic findings—at the sites of drug-eluting stent implantation, suggesting contrast staining outside the stent struts—that do not fulfill the classic definition of coronary artery aneurysm. We propose a new term, peri-stent contrast staining (PSS), for these abnormal angiographic findings and assess their incidence, risk factors, and clinical sequelae. Methods and Results— Peri-stent contrast staining was defined as contrast staining outside the stent contour extending to ≥20% of the stent diameter. The study population consisted of 3081 lesions (1998 patients) that were treated exclusively with sirolimus-eluting stents and were evaluated by follow-up angiography within 12 months after sirolimus-eluting stent implantation in a single center. Late acquired PSS was observed in 58 lesions (1.9%) in 49 patients (2.5%). Independent risk factors of PSS included chronic total occlusion, whereas negative risk factors for PSS were left circumflex coronary artery lesion and in-stent restenosis lesion. Stent fracture was more frequently observed in lesions with PSS than in lesions without PSS (43.1% versus 5.4%, P<0.0001). Excluding 269 lesions with target-lesion revascularization within 12 months, the study population for long-term follow-up consisted of 51 lesions (42 patients) with PSS and 2761 lesions (1751 patients) without PSS. Cumulative incidence of target-lesion revascularization and definite very late stent thrombosis at 3 years in the PSS group was higher than that in the non-PSS group (15.0% versus 6.5%, and 8.2% versus 0.2%, respectively). Conclusions— Peri-stent contrast staining found within 12 months after sirolimus-eluting stent implantation appeared to be associated with subsequent target-lesion revascularization and very late stent thrombosis.

Original ResearchOCT Compared With IVUS in a Coronary Lesion Assessment: The OPUS-CLASS Study

OBJECTIVES The aim of this study was to investigate the reliability of frequency domain optical coherence tomography (FD-OCT) for coronary measurements compared with quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). BACKGROUND Accurate luminal measurement is expected in FD-OCT because this technology offers high resolution and excellent contrast between lumen and vessel wall. METHODS In 5 medical centers, 100 patients with coronary artery disease were prospectively studied by using angiography, FD-OCT, and IVUS. In addition, 5 phantom models of known lumen dimensions (lumen diameter 3.08 mm; lumen area 7.45 mm(2)) were examined using FD-OCT and IVUS. Quantitative image analyses of the coronary arteries and phantom models were performed by an independent core laboratory. RESULTS In the clinical study, the mean minimum lumen diameter measured by QCA was significantly smaller than that measured by FD-OCT (1.81 ± 0.72 mm vs. 1.91 ± 0.69 mm; p < 0.001) and the minimum lumen diameter measured by IVUS was significantly greater than that measured by FD-OCT (2.09 ± 0.60 mm vs. 1.91 ± 0.69 mm; p < 0.001). The minimum lumen area measured by IVUS was significantly greater than that by FD-OCT (3.68 ± 2.06 mm(2) vs. 3.27 ± 2.22 mm(2); p < 0.001), although a significant correlation was observed between the 2 imaging techniques (r = 0.95, p < 0.001; mean difference 0.41 mm(2)). Both FD-OCT and IVUS exhibited good interobserver reproducibility, but the root-mean-squared deviation between measurements was approximately twice as high for the IVUS measurements compared with the FD-OCT measurements (0.32 mm(2) vs. 0.16 mm(2)). In a phantom model, the mean lumen area according to FD-OCT was equal to the actual lumen area of the phantom model, with low SD; IVUS overestimated the lumen area and was less reproducible than FD-OCT (8.03 ± 0.58 mm(2) vs. 7.45 ± 0.17 mm(2); p < 0.001). CONCLUSIONS The results of this prospective multicenter study demonstrate that FD-OCT provides accurate and reproducible quantitative measurements of coronary dimensions in the clinical setting.

Radioactive Stents Delay but Do Not Prevent In-Stent Neointimal Hyperplasia

Background—Restenosis after conventional stenting is almost exclusively caused by neointimal hyperplasia. &bgr;-Particle–emitting radioactive stents decrease in-stent neointimal hyperplasia at 6-month follow-up. The purpose of this study was to evaluate the 1-year outcome of 32P radioactive stents with an initial activity of 6 to 12 &mgr;Ci using serial quantitative coronary angiography and volumetric ECG-gated 3D intravascular ultrasound (IVUS). Methods and Results—Of 40 patients undergoing initial stent implantation, 26 were event-free after the 6-month follow-up period and 22 underwent repeat catheterization and IVUS at 1 year; they comprised half of the study population. Significant luminal deterioration was observed within the stents between 6 months and 1 year, as evidenced by a decrease in the angiographic minimum lumen diameter (−0.43±0.56 mm;P =0.028) and in the mean lumen diameter in the stent (−0.55±0.63 mm;P =0.001); a significant increase in in-stent neointimal hyperplasia by IVUS (18.16±12.59 mm3 at 6 months to 27.75±11.99 mm3 at 1 year;P =0.001) was also observed. Target vessel revascularization was performed in 5 patients (23%). No patient experienced late occlusion, myocardial infarction, or death. By 1 year, 21 of the initial 40 patients (65%) remained event-free. Conclusions—Neointimal proliferation is delayed rather than prevented by radioactive stent implantation. Clinical outcome 1 year after the implantation of stents with an initial activity of 6 to 12 &mgr;Ci is not favorable when compared with conventional stenting.

Sustained Suppression of Neointimal Proliferation by Sirolimus-Eluting Stents

Background We have previously reported a virtual absence of neointimal hyperplasia 4 months after implantation of sirolimus-eluting stents. The aim of the present investigation was to determine whether these results are sustained over a period of 1 year. Methods and Results Forty-five patients with de novo coronary disease were successfully treated with the implantation of a single sirolimus-eluting Bx VELOCITY stent in Sao Paulo, Brazil (n=30, 15 fast release [group I, GI] and 15 slow release [GII]) and Rotterdam, The Netherlands (15 slow release, GIII). Angiographic and volumetric intravascular ultrasound (IVUS) follow-up was obtained at 4 and 12 months (GI and GII) and 6 months (GIII). In-stent minimal lumen diameter and percent diameter stenosis remained essentially unchanged in all groups (at 12 months, GI and GII; at 6 months, GIII). Follow-up in-lesion minimal lumen diameter was 2.28 mm (GIII), 2.32 mm (GI), and 2.48 mm (GII). No patient approached the ≥50% diameter stenosis at 1 year by angiograp...