Masaki Awata

Serial Angioscopic Evidence of Incomplete Neointimal Coverage After Sirolimus-Eluting Stent Implantation Comparison With Bare-Metal Stents

Background— The time course of neointimal formation after stent implantation has not been studied extensively by angioscopy in the drug-eluting stent era. Methods and Results— Serial angioscopic findings at first follow-up (3.6±1.1 months), second follow-up (10.5±1.6 months), and third follow-up (21.2±2.2 months) after stent implantation were compared between sirolimus-eluting stents (SES, n=17) and bare-metal stents (BMS, n=11). Neointimal coverage, thrombus, and presence of yellow plaques underneath the stents were assessed. Neointimal coverage was graded as follows: grade 0, stent struts were fully visible; grade 1, struts bulged into the lumen, although they were covered; grade 2, struts were embedded by the neointima but were seen translucently; or grade 3, struts were fully embedded and invisible. Neointimal coverage was remarkably different between SES and BMS at each follow-up point. Neointimal coverage grade was 1.1±0.5 in SES versus 2.9±0.3 in BMS at the first follow-up (P<0.0001), 1.1±0.5 in SES versus 3.0±0.0 in BMS (P<0.0001) at the second follow-up, and 1.3±0.5 in SES versus 3.0±0.0 in BMS at the third follow-up (P=0.0009). No significant serial changes in coverage grade were noted in the BMS group, whereas coverage grade slightly but significantly increased at the third follow-up in the SES group (P<0.05). Thrombi were detected in 4 SES: a red thrombus was seen from the first to the third follow-up in 2; another was detected only at the third follow-up; and the fourth was seen at the first follow-up but disappeared at the second follow-up, associated with a new white thrombus despite dual antiplatelet therapy. Yellow plaques had disappeared by the time of the second follow-up in BMS. In contrast, yellow plaques were exposed in 71% of SES at the first follow-up and remained exposed until the third follow-up. Neointimal coverage grades correlated with thrombi (P=0.002) and with yellow plaques (P<0.0001). Conclusions— Serial angioscopic findings up to 2 years after SES implantation were markedly different from those after BMS. Neointimal coverage was completed by 3 to 6 months in BMS. In contrast, SES demonstrated the presence of thrombi and yellow plaques even as much as 2 years after 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.

Angioscopic Comparison of Neointimal Coverage Between Zotarolimus-and Sirolimus-Eluting Stents

Drug-eluting stents (DES) have demonstrated reduced late loss (LL) and low target lesion revascularization (TLR) rates through an inhibitory effect on neointimal hyperplasia but might have a risk of late or very late stent thrombosis due to incomplete neointimal coverage (NIC) ([1–3][1]). A

Heterogeneous arterial healing in patients following paclitaxel-eluting stent implantation: comparison with sirolimus-eluting stents.

OBJECTIVES We angioscopically compared paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) to explore differences in arterial healing. BACKGROUND Drug-eluting stents may demonstrate different arterial healing processes. METHODS Angioscopy was performed 9 +/- 2 months after 30 PES and 36 SES were implanted initially in the native coronary artery. Heterogeneity of the neointimal coverage (NIC) as well as the dominant grade was examined. Neointimal coverage was defined as follows: grade 0 = fully visible struts; grade 1 = struts bulged into the lumen, but covered; grade 2 = embedded, but translucent struts; grade 3 = invisible struts. Heterogeneity was judged when the NIC grade variation >or=1. Thrombi and yellow plaques (YP) were also explored. RESULTS In-stent late loss (0.44 +/- 0.44 mm vs. 0.13 +/- 0.33 mm; p < 0.0001) and dominant NIC grade (1.8 +/- 1.1 vs. 1.3 +/- 0.7; p = 0.02) were greater in PES than in SES. Of PES, 48% showed the heterogeneity of 1 grade; 26% showed that of 2 grades. Of SES, 53% showed homogeneous coverage; the remaining SES showed the heterogeneity of 1 grade; and 72% showed dominant grade 1. Thrombi were more common in PES than in SES (43% vs. 19%; p = 0.04). Both stents commonly revealed YP (83% vs. 78%; p = 0.76). CONCLUSIONS NIC was more heterogeneous in PES, associated with a higher incidence of thrombi. Homogeneous NIC may be an important factor for competent arterial healing.

Final 3-Year Outcome of a Randomized Trial Comparing Second-Generation Drug-Eluting Stents Using Either Biodegradable Polymer or Durable Polymer: NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial

Background—There is a paucity of data reporting the clinical outcomes of biodegradable polymer biolimus-eluting stent (BP-BES) compared with durable polymer everolimus-eluting stent (DP-EES) beyond 1 year after stent implantation when the polymer is fully degraded. Methods and Results—The NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial (NEXT) is a prospective, multicenter, randomized, open-label, noninferiority trial comparing BP-BES with DP-EES in patients scheduled for percutaneous coronary intervention using drug-eluting stent (DES) without any exclusion criteria among 98 participating centers in Japan. The trial was designed to evaluate noninferiority of BP-BES relative to DP-EES in terms of any target-lesion revascularization at 1 year and death or myocardial infarction at 3 years. Between May and October 2011, 3235 patients were randomly assigned to receive either BP-BES (1617 patients) or DP-EES (1618 patients). Complete 3-year follow-up was achieved in 97.6% of patients. At 3 years, the primary safety end point of death or myocardial infarction occurred in 159 patients (9.9%) in the BP-BES group and in 166 patients (10.3%) in the DP-EES group, demonstrating noninferiority of BP-BES relative to DP-EES (P noninferiority<0.0001 and P superiority=0.7). Cumulative incidence of target-lesion revascularization was not significantly different between the 2 groups (7.4% versus 7.1%; P=0.8). By a landmark analysis at 1 year, the cumulative incidences of death or myocardial infarction and target-lesion revascularization were also not significantly different between the 2 groups (4.6% versus 5.2%; P=0.46 and 3.3% versus 2.7%; P=0.39, respectively). Conclusions—Safety and efficacy outcomes of BP-BES were non inferior to those of DP-EES 3 years after stent implantation. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01303640.

Three-Year Clinical Outcomes of Everolimus-Eluting Stents From the Post-Marketing Surveillance Study of Cobalt-Chromium Everolimus-Eluting Stent (XIENCE V/PROMUS) in Japan

BACKGROUND The Cobalt-Chromium Everolimus-Eluting Stent (CoCr-EES) Post-marketing Surveillance (PMS) is a prospective multicenter registry designed to evaluate the safety and efficacy of XIENCE V/PROMUS everolimus-eluting stents in routine clinical practice at 47 centers representative of the clinical environment in Japan. METHODSANDRESULTS We enrolled 2,010 consecutive patients (2,649 lesions) who underwent PCI using CoCr-EES. Clinical outcomes were evaluated for up to 3 years. Clinical follow-up was available in 1,930 patients (96%) at 3 years. Major adverse cardiovascular events (MACE) occurred in 6.8% of patients, including cardiac death (1.7%), myocardial infarction (1.5%), and clinically driven target lesion revascularization (CD-TLR, 4.2%). Late CD-TLR rate was 0.8% from 1 to 2 years, and 0.5% from 2 to 3 years. Definite or probable stent thrombosis occurred in 7 patients (0.3%) up to 1 year. There was no very late definite or probable stent thrombosis from 1 to 3 years. Significant independent predictors for MACE were hemodialysis, prior coronary intervention, triple-vessel coronary artery disease, and age >70 years. CONCLUSIONS Three-year clinical outcomes from the CoCr-EES PMS demonstrated a low incidence of clinical events. There was no major concern about very late stent thrombosis or late catch-up phenomenon in patients treated with EES in routine clinical practice in Japan.

Objective Interpretation of Dobutamine Stress Echocardiography by Diastolic Dyssynchrony Imaging: A Practical Approach

BACKGROUND Postsystolic shortening is a sensitive maker of myocardial ischemia. The aim of this study was to investigate whether diastolic dyssynchrony imaging is useful for the objective interpretation of dobutamine stress echocardiography. METHODS Postsystolic shortening was detected by using tissue Doppler imaging displacement timing analysis: the delays of the displacement peaks from end-systole were displayed from green to red, depending on the preset time window on diastolic dyssynchrony imaging. Dobutamine stress echocardiography was performed in 59 patients with suspected coronary artery disease who presented with normal left ventricular wall motion at rest (age range, 44-83 years; 20 women). The optimal time windows for diastolic dyssynchrony imaging at rest and at peak dobutamine were determined by receiver operating characteristic analysis by measuring the delays of the displacement peaks in the left ventricular myocardial segments. Diastolic dyssynchrony imaging was performed using time windows of 100 msec at rest and 80 msec at peak dobutamine. The diagnostic power of diastolic dyssynchrony imaging was assessed with quantitative coronary angiography as the gold standard (>50% diameter stenosis) both at rest and at peak dobutamine. RESULTS Coronary artery disease was present in 37 patients (63%). Diastolic dyssynchrony imaging at peak dobutamine predicted the presence of coronary artery disease with sensitivity of 89%, specificity of 77%, predictive accuracy of 85%, positive predictive value of 79%, and negative predictive value of 81%. Diastolic dyssynchrony imaging at rest yielded sensitivity of 62%, specificity of 73%, predictive accuracy of 66%, positive predictive value of 79%, and negative predictive value of 53%. Importantly, diastolic dyssynchrony imaging demonstrated excellent intraindividual (97%) and interindividual (90%) agreement. CONCLUSION Diastolic dyssynchrony imaging is useful in the objective interpretation of dobutamine stress echocardiography.

Three-year follow-up outcomes of SES and PES in a randomized controlled study stratified by the presence of diabetes mellitus: J-DEsSERT trial

BACKGROUND Three-year clinical follow-up of patients with diabetes mellitus (DM) in the Japan-Drug Eluting Stents Evaluation; a Randomized Trial (J-DESsERT) using 2 different drug eluting stents (DES). A recent study demonstrated that efficacy of sirolimus eluting stents (SES) attenuated over time in diabetic patients. METHODS In the largest trial of its kind, 1724 DM patients out of 3533 enrolled patients were randomized to either SES or paclitaxel eluting stents (PES). RESULTS There were no significant differences in baseline clinical characteristics aside from hypertension. Incidence of major adverse cardiac cerebrovascular events (MACCE) mainly due to higher target vessel failure (TVF) initially indicated a benefit in SES (MACCE rate at 1 year: SES 9.4%, PES 12.2%, p=0.08); however this had attenuated by the time of the 3-year follow-up (MACCE rate from 1 to 3 years: SES 8.4%, PES 6.1%, p=0.10). A similar pattern was observed in insulin-treated patients: MACCE rate from 1 to 3 years was 10.5% in SES and 6.4% in PES (p=0.25). Angiographic follow-up also resulted in higher major adverse cardiac event (MACE) rates at 1 year (presence 11.5%, absence 8.3%, p=0.04); however by 3 years rates were similar regardless of the presence of angiographic follow-up (MACE rate at 3 years: presence 16.0%, absence 14.5%, p=0.35). CONCLUSIONS The superiority of SES over PES in MACCE at 1 year had attenuated by 3-year follow-up. Eventually, the 3-year safety and efficacy profiles were similar regardless of insulin treatment.

Very Late Stent Thrombosis 5 Years After Implantation of a Sirolimus-Eluting Stent Observed by Angioscopy and Optical Coherence Tomography

Drug-eluting stents have dramatically reduced the rate of in-stent restenosis ([1][1]). However, very late stent thrombosis (VLST) is one of the clinical issues with regard to the safety of drug-eluting stents ([2,3][2]). To date there are no articles that report VLST evaluated by both angioscopy

Efficient distal tip size of primary guidewire for antegrade percutaneous coronary intervention in chronic total occlusion: The G-FORCE study.

BACKGROUND Although several new techniques have been introduced for CTO such as the retrograde approach, the fundamental question of what type of guidewire is the most appropriate as a primary guidewire in the antegrade approach has not been answered. METHODS The G-FORCE study was designed as a prospective multicenter randomized controlled trial to determine the efficient primary guidewire in antegrade approach for chronic total occlusion (CTO). The first guidewire was randomly assigned to a regular size distal tip group (0.014in. size) or tapered tip group (0.010in. or less). The primary endpoint was defined as successful lesion penetration by the first guidewire into distal true lumen. This study was registered at ClinicalTrials.gov with identifier NCT00987610. RESULTS A total of 260 patients were enrolled, with an average age of 66±11years and 16% were female. The average J-CTO score was 1.8±1.1. The primary endpoint was achieved in 38% and 32% of patients using tapered and regular distal tip guidewires, respectively (P=0.80). The final PCI success rate was 81% vs. 85%, respectively (P=0.57). Easy CTO lesions with a J-CTO score=0 exhibited a primary endpoint significantly different between tapered and regular distal tip primary guidewires (79% vs. 40%; P=0.046). Guidewire distal coating or distal tip load did not relate with primary guidewire success rate. CONCLUSION Tapered and regular distal tip guidewires are equivalent as a first choice for CTO. Tapered guidewires are superior for CTO lesions with a J-CTO score=0.