Masahiro Natsuaki

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.

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.

Late Adverse Events After Implantation of Sirolimus-Eluting Stent and Bare-Metal Stent Long-Term (5–7 Years) Follow-Up of the Coronary Revascularization Demonstrating Outcome Study-Kyoto Registry Cohort-2

Background—Late adverse events such as very late stent thrombosis (VLST) or late target-lesion revascularization (TLR) after first-generation sirolimus-eluting stents (SES) implantation have not been yet fully characterized at long term in comparison with those after bare-metal stent (BMS) implantation. Methods and Results—Among 13 058 consecutive patients undergoing first percutaneous coronary intervention in the Coronary REvascularization Demonstrating Outcome study-Kyoto registry Cohort-2, 5078 patients were treated with SES only, and 5392 patients were treated with BMS only. During 7-year follow-up, VLST and late TLR beyond 1 year after SES implantation occurred constantly and without attenuation at 0.24% per year and at 2.0% per year, respectively. Cumulative 7-year incidence of VLST was significantly higher in the SES group than that in the BMS group (1.43% versus 0.68%, P<0.0001). However, there was no excess of all-cause death beyond 1 year in the SES group as compared with that in the BMS group (20.8% versus 19.6%, P=0.91). Cumulative incidences of late TLR (both overall and clinically driven) were also significantly higher in the SES group than in the BMS group (12.0% versus 4.1%, P<0.0001 and 8.5% versus 2.6%, P<0.0001, respectively), leading to late catch-up of the SES group to the BMS group regarding TLR through the entire 7-year follow-up (18.8% versus 25.2%, and 10.6% versus 10.2%, respectively). Clinical presentation as acute coronary syndrome was more common at the time of late SES TLR compared with early SES TLR (21.2% and 10.0%). Conclusions—Late catch-up phenomenon regarding stent thrombosis and TLR was significantly more pronounced with SES than that with BMS. This limitation should remain the target for improvements of DES technology.

Long-term outcomes after percutaneous coronary intervention for chronic total occlusion (from the CREDO-Kyoto registry cohort-2).

Despite improving success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions, the clinical benefit of recanalization of CTO is still a matter of debate. Of 13,087 patients who underwent PCI in the CREDO-Kyoto registry cohort-2, 1,524 patients received PCI for CTO (CTO-PCI). Clinical outcomes were compared between 1,192 patients with successful CTO-PCI and 332 patients with failed CTO-PCI. In-hospital death tended to occur less frequently in the successful CTO-PCI group than in the failed CTO-PCI group (1.4% vs 3.0%, p = 0.053). Through 3-year follow-up, the cumulative incidence of all-cause death was not significantly different between the successful and failed CTO-PCI groups (9.0% vs 13.1%, p = 0.18), whereas the cumulative incidence of cardiac death was significantly less in the successful CTO-PCI group than in the failed CTO-PCI group (4.5% vs 8.4%, p = 0.03). However, after adjusting confounders, successful CTO-PCI was associated with lesser risk for neither all-cause death (hazard ratio 0.93, 95% confidence interval 0.64 to 1.37, p = 0.69) nor cardiac death (hazard ratio 0.71, 95% confidence interval 0.44 to 1.16, p = 0.16). The cumulative incidence of coronary artery bypass grafting (CABG) was remarkably less in patients with successful PCI compared with those with failed PCI (1.8% vs 19.6%, p <0.0001). In conclusion, successful CTO-PCI compared with failed PCI was not associated with lesser risk for 3-year mortality. However, successful CTO-PCI was associated with significantly less subsequent CABG.

Duration of Dual Antiplatelet Therapy and Long-Term Clinical Outcome After Coronary Drug-Eluting Stent Implantation Landmark Analyses From the CREDO-Kyoto PCI/CABG Registry Cohort-2

Background— Optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation has not been yet fully elucidated. Methods and Results— We assessed the influence of prolonged thienopyridine therapy on clinical outcomes with landmark analysis at 4 and 13 months after DES implantation. Among 6802 patients with at least 1 DES implantation in the CREDO-Kyoto Registry Cohort-2, 6309 patients (on thienopyridine, 5438 patients; off thienopyridine, 871 patients) and 5901 patients (on thienopyridine, 4098 patients; off thienopyridine, 1803 patients) were eligible for the 4- and 13-month landmark analyses, respectively. The majority of patients had stable coronary artery disease (73%) and received sirolimus-eluting stents (93%), and approximately 90% of thienopyridine was ticlopidine. Patients taking thienopyridine had more complex comorbidities and more complex lesion and procedural characteristics as compared with patients not taking thienopyridine. After adjusting for confounders, thienopyridine use was not associated with decreased risk for death/myocardial infarction/stroke (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.89–1.43, P=0.32 in the 4-month landmark analysis; HR, 1.14; 95% CI, 0.90–1.45, P=0.29 in the 13-month landmark analysis, respectively), whereas the risk for GUSTO moderate/severe bleeding tended to be higher in patients taking thienopyridine (HR, 1.51; 95% CI, 1.00–2.23, P=0.049 in the 4-month landmark analysis; HR, 1.44; 95% CI, 0.99–2.09, P=0.057 in the 13-month landmark analysis, respectively). Conclusions— Prolonged thienopyridine therapy beyond 4 and 13 months appeared not to be associated with reduction in ischemic events but to be associated with a trend toward increased bleeding. Optimal duration of DAPT after DES implantation might be shorter than the currently recommended 1-year interval.

Two-Year Outcome of a Randomized Trial Comparing Second-Generation Drug-Eluting Stents Using Biodegradable or Durable Polymer

Recent network meta-analyses have raised concerns about the safety of biodegradable polymer drug-eluting stents (BP-DES) compared with durable polymer everolimus-eluting stents (DP-EES).1- 3 The NOBORI Biolimus-Eluting vs XIENCE/PROMUS Everolimus-Eluting Stent Trial (NEXT) is a 98-center, randomized, open-label, noninferiority trial evaluating the efficacy and safety of biodegradable polymer biolimus-eluting stents (BP-BES) vs DP-EES.4

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.

Comparison of Long-Term Outcome After Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Unprotected Left Main Coronary Artery Disease (from the CREDO-Kyoto PCI/CABG Registry Cohort-2)

The long-term outcome of percutaneous coronary intervention (PCI) compared to coronary artery bypass grafting (CABG) for unprotected left main coronary artery disease (ULMCAD) remains to be investigated. We identified 1,005 patients with ULMCAD of 15,939 patients with first coronary revascularization enrolled in the CREDO-Kyoto PCI/CABG Registry Cohort-2. Cumulative 3-year incidence of a composite of death/myocardial infarction (MI)/stroke was significantly higher in the PCI group than in the CABG group (22.7% vs 14.8%, p = 0.0006, log-rank test). However, the adjusted outcome was not different between the PCI and CABG groups (hazard ratio [HR] 1.30, 95% confidence interval [CI] 0.79 to 2.15, p = 0.30). Stratified analysis using the SYNTAX score demonstrated that risk for a composite of death/MI/stroke was not different between the 2 treatment groups in patients with low (<23) and intermediate (23 to 33) SYNTAX scores (adjusted HR 1.70, 95% CI 0.77 to 3.76, p = 0.19; adjusted HR 0.86, 95% CI 0.37 to 1.99, p = 0.72, respectively), whereas in patients with a high SYNTAX score (≥33), it was significantly higher after PCI than after CABG (adjusted HR 2.61, 95% CI 1.32 to 5.16, p = 0.006). In conclusion, risk of PCI for serious adverse events seemed to be comparable to that after CABG in patients with ULMCAD with a low or intermediate SYNTAX score, whereas PCI compared with CABG was associated with a higher risk for serious adverse events in patients with a high SYNTAX score.

β-blocker use in patients after percutaneous coronary interventions: one size fits all? Worse outcomes in patients without myocardial infarction or heart failure.

BACKGROUND The influence of β-blocker therapy on prognosis in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) has not been fully explored. METHODS AND RESULTS We identified 5288 CAD patients who did not have myocardial infarction (MI) or heart failure (HF) but underwent PCI from a large multi-center registry enrolling consecutive patients undergoing first coronary revascularization from 2005 to 2007. The primary outcome was a composite endpoint of cardiac death and/or MI (cardiac death/MI) at 3 years after hospital discharge for PCI. β-blockers were prescribed in 1117 patients (β group, 21.1%) at discharge, while 4171 patients did not (no-β group, 78.9%). Patients in the β group more often had hypertension, multivessel disease, use of statin and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, but less often had chronic obstructive pulmonary disease. The 3-year incidence of cardiac death/MI was higher in the β group (4.9% vs. 3.4%, log-rank p=0.02). After adjusting for potential confounders, β-blocker therapy was associated with significantly increased risk for cardiac death/MI (hazard ratio 1.48, 95% confidence interval 1.05-2.10, p=0.02). CONCLUSIONS β-blocker therapy was associated with worse 3-year clinical outcomes in CAD patients who underwent PCI but had no history of MI or HF. Randomized trials are warranted to identify appropriate subsets of patients who could truly benefit from long-term use of β-blockers in this setting.

Impact of Statin Therapy on Late Target Lesion Revascularization After Sirolimus-Eluting Stent Implantation (from the CREDO-Kyoto Registry Cohort-2)

Therapeutic strategies preventing late target lesion revascularization (TLR) after drug-eluting stent implantation have not been yet adequately investigated. In 13,087 consecutive patients undergoing first percutaneous coronary intervention in the CREDO-Kyoto Registry Cohort-2, we identified 10,221 patients who were discharged alive after implantation of sirolimus-eluting stents (SESs) only (SES stratum 5,029) or bare-metal stents (BMSs) only (BMS stratum 5,192). Impact of statin therapy at time of discharge from the index hospitalization on early (within the first year) and late (1 year to 4 years) TLR, was assessed in the SES stratum (statin group 2,735; nonstatin group 2,294) and in the BMS stratum (statin group 2,576; nonstatin group 2,616). Despite a significantly lower incidence of early TLR (7.8% vs 22.2%, p <0.0001), SES use compared to BMS use was associated with a significantly higher incidence of late TLR (7.7% vs 3.0%, p <0.0001). In the SES and BMS strata, the incidence of early TLR was similar regardless of statin use. In the SES stratum, the incidence of late TLR was significantly lower in the statin group than in the nonstatin group (6.1% vs 9.6%, p = 0.002), whereas no significant difference was found in the BMS stratum (2.6% vs 3.3%, p = 0.38). After adjusting confounders, risk for late TLR significantly favored statin use in the SES stratum (hazard ratio 0.73, 95% confidence interval 0.54 to 0.98, p = 0.04), whereas the risk decrease was not significant in the BMS stratum (hazard ratio 0.74, 95% confidence interval 0.46 to 1.20, p = 0.23). In conclusion, statin therapy at hospital discharge was associated with a significantly lower risk for late TLR after SES implantation.