Clinical outcome of patients with and without diabetes mellitus after percutaneous coronary intervention with the resolute zotarolimus-eluting stent: 2-year results from the prospectively pooled analysis of the international global RESOLUTE program.

The aim of this study was to describe the process to obtain Food and Drug Administration (FDA) approval for the expanded indication for treatment with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Inc., Santa Rosa, California) in patients with coronary artery disease and diabetes. The R-ZES is the first drug-eluting stent specifically indicated in the United States for percutaneous coronary intervention in patients with diabetes. We pooled patient-level data for 5,130 patients from the RESOLUTE Global Clinical Program. A performance goal prospectively determined in conjunction with the FDA was established as a rate of target vessel failure at 12 months of 14.5%. In addition to the FDA pre-specified cohort of less complex patients with diabetes (n = 878), we evaluated outcomes of the R-ZES in all 1,535 patients with diabetes compared with all 3,595 patients without diabetes at 2 years. The 12-month rate of target vessel failure in the pre-specified diabetic cohort was 7.8% (upper 95% confidence interval: 9.51%), significantly lower than the performance goal of 14.5% (p < 0.001). After 2 years, the cumulative incidence of target lesion failure in patients with noninsulin-treated diabetes was comparable to that of patients without diabetes (8.0% vs. 7.1%). The higher risk insulin-treated population demonstrated a significantly higher target lesion failure rate (13.7%). In the whole population, including complex patients, rates of stent thrombosis were not significantly different between patients with and without diabetes (1.2% vs. 0.8%). The R-ZES is safe and effective in patients with diabetes. Long-term clinical data of patients with noninsulin-treated diabetes are equivalent to patients without diabetes. Patients with insulin-treated diabetes remain a higher risk subset. (The Medtronic RESOLUTE Clinical Trial; NCT00248079; Randomized, Two-arm, Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent [RESOLUTE-AC]; NCT00617084; The Medtronic RESOLUTE US Clinical Trial (R-US); NCT00726453; RESOLUTE International Registry: Evaluation of the Resolute Zotarolimus-Eluting Stent System in a 'Real-World' Patient Population [R-Int]; NCT00752128; RESOLUTE Japan-The Clinical Evaluation of the MDT-4107 Drug-Eluting Coronary Stent [RJ]; NCT00927940).

Silber S ，Serruys PW ，Leon MB ，Meredith IT ，Windecker S ，Neumann FJ ，Belardi J ，Widimsky P ，Massaro J ，Novack V ，Yeung AC ，Saito S ，Mauri L ... -  《-》

Differential Prognostic Effect Between First- and Second-Generation Drug-Eluting Stents in Coronary Bifurcation Lesions: Patient-Level Analysis of the Korean Bifurcation Pooled Cohorts.

The purpose of this study was to investigate the differential clinical outcomes after percutaneous coronary intervention (PCI) for coronary bifurcation lesions with 1- or 2-stenting techniques using first- or second-generation drug-eluting stents (DES). The 2-stenting technique has been regarded to have worse clinical outcomes than the 1-stenting technique after bifurcation PCI with first-generation DES. However, there has been a paucity of data comparing the 1- and 2-stenting techniques with the use of second-generation DES. Patient-level pooled analysis was performed with 3,162 patients undergoing PCI using first- or second-generation DES for bifurcation lesions from the "Korean Bifurcation Pooled Cohorts" (COBIS [Coronary Bifurcation Stenting] II, EXCELLENT [Registry to Evaluate Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting], and RESOLUTE-Korea [Registry to Evaluate the Efficacy of Zotarolimus-Eluting Stent]). The 3-year clinical outcomes were compared between 1- and 2-stenting techniques, stratified by the type of DES. With first-generation DES, rates of target lesion failure (TLF) or patient-oriented composite outcome (POCO) (a composite of all death, any myocardial infarction, any repeat revascularization, and cerebrovascular accidents) at 3 years were significantly higher after the 2-stenting than the 1-stenting technique (TLF 8.6% vs. 17.5%; p < 0.001; POCO 18.1% vs. 28.5%, p < 0.001). With second-generation DES, however, there was no difference between 1- and 2-stenting techniques (TLF 5.4% vs. 5.8%; p = 0.768; POCO 11.2% vs. 12.9%; p = 0.995). The differential effects of 2-stenting technique on the prognosis according to the type of DES were also corroborated with similar results by the inverse probability weighted model. The 2-stenting technique was a significant independent predictor of TLF in first-generation DES (hazard ratio: 2.046; 95% confidence interval: 1.114 to 3.759; p < 0.001), but not in second-generation DES (hazard ratio: 0.667; 95% confidence interval: 0.247 to 1.802; p = 0.425). Patient-level pooled analysis of 3,162 patients in Korean Bifurcation Pooled Cohorts demonstrated that the 2-stenting technique showed comparable outcomes to 1-stenting technique with second-generation DES, which is different from the results of first-generation DES favoring the 1-stenting technique.

Lee JM ，Hahn JY ，Kang J ，Park KW ，Chun WJ ，Rha SW ，Yu CW ，Jeong JO ，Jeong MH ，Yoon JH ，Jang Y ，Tahk SJ ，Gwon HC ，Koo BK ，Kim HS ... -  《-》

Impact of lesion length and vessel size on clinical outcomes after percutaneous coronary intervention with everolimus- versus paclitaxel-eluting stents pooled analysis from the SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent

The aim of this study was to investigate the impact of reference vessel diameter (RVD) and lesion length (LL) on the relative safety and efficacy of everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES). Lesion length and RVD are well-known predictors of adverse events after percutaneous coronary intervention. Patient-level data were pooled from the randomized SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) II, III, IV and COMPARE (Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice) trials. Quantitative angiographic core laboratory data were available for 6,183 patients randomized to EES (n = 3,944) or PES (n = 2,239). Long lesions and small vessels were defined as LL >median (13.4 mm) and RVD ≤median (2.65 mm), respectively. Major adverse cardiac events (MACE) (consisting of cardiac death, myocardial infarction, or ischemia-driven target lesion revascularization) were assessed at 2 years, according to stent type in 3 groups: short lesions in large vessels (group A, n = 1,297); long lesions or small vessels but not both (group B, n = 2,981); and long lesions in small vessels (group C, n = 1,905). The pooled 2-year MACE rates were 5.6%, 8.2%, and 10.4% in Groups A, B, and C, respectively (p < 0.0001). There was no significant interaction between lesion group and stent type (p = 0.64), indicating lower MACE with EES compared with PES regardless of LL and RVD. However, the absolute difference was largest in Groups B and C. In Group A, 2-year MACE rates were not significantly different between EES and PES (4.8% vs. 7.0%, respectively, p = 0.11). In contrast, EES was associated with lower 2-year rates of MACE in Group B (6.6% vs. 11.2%, p < 0.01) and in Group C (9.1% vs. 12.7%, p = 0.008) as well as lower rates of myocardial infarction, target lesion revascularization, and stent thrombosis. Multivariable analysis confirmed EES versus PES as an independent predictor of freedom from MACE in Groups B and C. Patients with short lesions in large vessels have low rates of MACE at 2 years after treatment with either EES or PES. In higher-risk patients with long lesions and/or small vessels, EES results in significant improvements in both clinical safety and efficacy outcomes. (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions; NCT00180310; SPIRIT III: A Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System [EECSS] in the Treatment of Subjects With de Novo Native Coronary Artery Lesions; NCT00180479; SPIRIT IV Clinical Trial: Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions; NCT00307047; A Randomized Controlled Trial of Everolimus-eluting Stents and Paclitaxel-eluting Stents for Coronary Revascularization in Daily Practice: The COMPARE Trial; NCT01016041).

Claessen BE ，Smits PC ，Kereiakes DJ ，Parise H ，Fahy M ，Kedhi E ，Serruys PW ，Lansky AJ ，Cristea E ，Sudhir K ，Sood P ，Simonton CA ，Stone GW ... -  《-》

Safety and efficacy of a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent for the treatment of de novo coronary lesions: two-year results from a prospective patient-level pooled analysis of TARGET trials.

We aimed to evaluate the safety and effectiveness of the novel abluminal groove-filled biodegradable polymer-coated sirolimus-eluting FIREHAWK stent (MicroPort Medical, Shanghai, China) in a large cohort of patients. Trials on the FIREHAWK stent allowing targeted sirolimus release were not individually powered to reliably estimate low-frequency safety endpoints such as stent thrombosis (ST) or to examine long-term safety and efficacy. Additionally, the China Food and Drug Administration requires an objective performance criterion (OPC) study for new drug-eluting stents. The primary endpoint, target lesion failure (TLF), was defined as the composite of cardiac death, target vessel myocardial infarction (MI), or clinically indicated target lesion revascularization at 12 months. Patient-level data from 1,007 patients with de novo native coronary lesions exclusively treated with the FIREHAWK stent in the TARGET serial studies (I and II) were prospectively collected, pooled and analyzed throughout a 2-year follow-up. The 12-month rate of TLF in 1,003 patients (follow-up rate, 99.6%) was 3.9% (upper 95% confidence interval (CI): 5.3%), which was significantly lower than the performance goal of 9.0% (P < 0.0001). The 24-month rates of TLF, PoCE (a composite of all-cause death, all MI, or any revascularization), and ARC definite or probable ST were 4.6%, 7.8% and 0.1%, respectively. In subgroup analysis, long lesion (≥ 30 mm) was an independent predictor of TLF within 2 years (hazard ratio [95%CI]: 2.44 [1.32, 4.53], P < 0.01). This pooled, patient-level analysis indicates that the FIREHAWK stent exhibits a promising 2-year efficacy and safety profile.

Gao Z ，Zhang R ，Xu B ，Yang Y ，Ma C ，Li H ，Chen S ，Han Y ，Yuan Z ，Lansky AJ ，Guan C ，Leon MB ，Gao R ，TARGET Investigators ... -  《-》

Comparison of newer-generation drug-eluting with bare-metal stents in patients with acute ST-segment elevation myocardial infarction: a pooled analysis of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) and COMFO

This study sought to study the efficacy and safety of newer-generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in an appropriately powered population of patients with ST-segment elevation myocardial infarction (STEMI). Among patients with STEMI, early generation DES improved efficacy but not safety compared with BMS. Newer-generation DES, everolimus-eluting stents, and biolimus A9-eluting stents, have been shown to improve clinical outcomes compared with early generation DES. Individual patient data for 2,665 STEMI patients enrolled in 2 large-scale randomized clinical trials comparing newer-generation DES with BMS were pooled: 1,326 patients received a newer-generation DES (everolimus-eluting stent or biolimus A9-eluting stent), whereas the remaining 1,329 patients received a BMS. Random-effects models were used to assess differences between the 2 groups for the device-oriented composite endpoint of cardiac death, target-vessel reinfarction, and target-lesion revascularization and the patient-oriented composite endpoint of all-cause death, any infarction, and any revascularization at 1 year. Newer-generation DES substantially reduce the risk of the device-oriented composite endpoint compared with BMS at 1 year (relative risk [RR]: 0.58; 95% confidence interval [CI]: 0.43 to 0.79; p = 0.0004). Similarly, the risk of the patient-oriented composite endpoint was lower with newer-generation DES than BMS (RR: 0.78; 95% CI: 0.63 to 0.96; p = 0.02). Differences in favor of newer-generation DES were driven by both a lower risk of repeat revascularization of the target lesion (RR: 0.33; 95% CI: 0.20 to 0.52; p < 0.0001) and a lower risk of target-vessel infarction (RR: 0.36; 95% CI: 0.14 to 0.92; p = 0.03). Newer-generation DES also reduced the risk of definite stent thrombosis (RR: 0.35; 95% CI: 0.16 to 0.75; p = 0.006) compared with BMS. Among patients with STEMI, newer-generation DES improve safety and efficacy compared with BMS throughout 1 year. It remains to be determined whether the differences in favor of newer-generation DES are sustained during long-term follow-up.

Sabaté M ，Räber L ，Heg D ，Brugaletta S ，Kelbaek H ，Cequier A ，Ostojic M ，Iñiguez A ，Tüller D ，Serra A ，Baumbach A ，von Birgelen C ，Hernandez-Antolin R ，Roffi M ，Mainar V ，Valgimigli M ，Serruys PW ，Jüni P ，Windecker S ... -  《-》