Safety and Efficacy of Polymer-Free Biolimus A9-Coated Versus Bare-Metal Stents in Orally Anticoagulated Patients: 2-Year Results of the LEADERS FREE Oral Anticoagulation Substudy.

The aim of this study was to compare the performance of drug-coated stents (DCS) versus bare-metal stents (BMS) in patients who are candidates for long-term oral anticoagulation (OAC) after percutaneous coronary interventions. The randomized controlled LEADERS FREE (A Randomized Clinical Evaluation of the BioFreedom™ Stent) trial demonstrated the superior safety and efficacy of a polymer-free biolimus A9 DCS compared with a similar BMS used with 1 month of dual antiplatelet therapy in 2,466 patients at high bleeding risk. The 2 stents were compared in a pre-specified analysis of the 879 LEADERS FREE patients (35.6%) scheduled to remain on OAC after percutaneous coronary intervention. The primary safety endpoint was a composite of cardiac death, myocardial infarction, and stent thrombosis. The primary efficacy endpoint was the incidence of clinically driven target lesion revascularization. Baseline characteristics of 448 DCS and 431 BMS recipients were similar, 78.8% had histories of atrial fibrillation, and 21% presented with acute coronary syndromes. Four hundred patients in the DCS group and 376 in the BMS group were discharged on OAC after percutaneous coronary intervention. At 2 years, for the DCS and BMS recipients, respectively, the incidence of clinically driven target lesion revascularization was 7.5% versus 11.2% (hazard ratio: 0.63; 95% confidence interval: 0.40 to 1.01; p = 0.0514), the safety endpoint was reached by 14.4% and 15.0% (p = NS), and the rates of major bleeding events (Bleeding Academic Research Consortium 3 to 5) were 10.7% and 12.9% (p = NS). The efficacy advantage of DCS over BMS up to 2 years appears confirmed in patients on long-term OAC. Despite the very short course of dual antiplatelet therapy, both the DCS and BMS groups experienced similarly high rates of major bleeding. (A Randomized Clinical Evaluation of the BioFreedom™ Stent [Leaders Free]; NCT01623180).

Carrié D ，Menown I ，Oldroyd K ，Copt S ，Talwar S ，Maillard L ，Morice MC ，Teik LS ，Lang I ，Urban P ... -  《-》

2-Year Outcomes of High Bleeding Risk Patients After Polymer-Free Drug-Coated Stents.

A 1-year follow-up, polymer-free metallic stent coated with biolimus-A9 followed by 1-month dual antiplatelet therapy is safer and more effective than a bare-metal stent (BMS) for patients with high risk of bleeding. This study analyzed 2-year outcomes to determine whether these benefits are maintained. In a prospective, multicenter, double-blind trial, we randomized 2,466 high bleeding risk patients to receive a drug-coated stent (DCS) or a BMS followed by 1-month dual antiplatelet therapy. The primary safety endpoint was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy endpoint was clinically driven target lesion revascularization. At 2 years, the primary safety endpoint had occurred in 147 DCS and 180 BMS patients (15.3%) (hazard ratio: 0.80; 95% confidence interval: 0.64 to 0.99; p = 0.039). Clinically driven target lesion revascularization occurred for 77 DCS and 136 BMS patients (12.0%) (hazard ratio: 0.54; 95% confidence interval: 0.41 to 0.72; p < 0.0001). Major bleeding occurred in 8.9% of DCS and 9.2% of BMS patients (p = 0.95), and a coronary thrombotic event (myocardial infarction and/or stent thrombosis) occurred in 8.2% of DCS and 10.6% of BMS patients (p = 0.045). One-year mortality was 27.1% for a major bleed and 26.3% for a thrombotic event. At 2 years, multivariate correlates of major bleeding were age >75 years, anemia, raised plasma creatinine, and planned long-term anticoagulation. Correlates of the primary safety endpoint were age, anemia, congestive heart failure, multivessel disease, number of stents implanted, and use of a BMS rather than a DCS. Safety and efficacy benefits of DCS over BMS were maintained for 2 years in high bleeding risk patients. Rates of major bleeding and coronary thrombotic events were no different and were associated with a substantial and comparable mortality risk. (A Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug Coated Stent Versus the Gazelle Bare Metal Stent in Patients With High Risk of Bleeding [LEADERS FREE]; NCT01623180).

Garot P ，Morice MC ，Tresukosol D ，Pocock SJ ，Meredith IT ，Abizaid A ，Carrié D ，Naber C ，Iñiguez A ，Talwar S ，Menown IBA ，Christiansen EH ，Gregson J ，Copt S ，Hovasse T ，Lurz P ，Maillard L ，Krackhardt F ，Ong P ，Byrne J ，Redwood S ，Windhövel U ，Greene S ，Stoll HP ，Urban P ，LEADERS FREE Investigators ... -  《-》

Improved safety and reduction in stent thrombosis associated with biodegradable polymer-based biolimus-eluting stents versus durable polymer-based sirolimus-eluting stents in patients with coronary artery disease: final 5-year report of the LEADERS (Limus

This study sought to report the final 5 years follow-up of the landmark LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) trial. The LEADERS trial is the first randomized study to evaluate biodegradable polymer-based drug-eluting stents (DES) against durable polymer DES. The LEADERS trial was a 10-center, assessor-blind, noninferiority, "all-comers" trial (N = 1,707). All patients were centrally randomized to treatment with either biodegradable polymer biolimus-eluting stents (BES) (n = 857) or durable polymer sirolimus-eluting stents (SES) (n = 850). The primary endpoint was a composite of cardiac death, myocardial infarction (MI), or clinically indicated target vessel revascularization within 9 months. Secondary endpoints included extending the primary endpoint to 5 years and stent thrombosis (ST) (Academic Research Consortium definition). Analysis was by intention to treat. At 5 years, the BES was noninferior to SES for the primary endpoint (186 [22.3%] vs. 216 [26.1%], rate ratio [RR]: 0.83 [95% confidence interval (CI): 0.68 to 1.02], p for noninferiority <0.0001, p for superiority = 0.069). The BES was associated with a significant reduction in the more comprehensive patient-orientated composite endpoint of all-cause death, any MI, and all-cause revascularization (297 [35.1%] vs. 339 [40.4%], RR: 0.84 [95% CI: 0.71 to 0.98], p for superiority = 0.023). A significant reduction in very late definite ST from 1 to 5 years was evident with the BES (n = 5 [0.7%] vs. n = 19 [2.5%], RR: 0.26 [95% CI: 0.10 to 0.68], p = 0.003), corresponding to a significant reduction in ST-associated clinical events (primary endpoint) over the same time period (n = 3 of 749 vs. n = 14 of 738, RR: 0.20 [95% CI: 0.06 to 0.71], p = 0.005). The safety benefit of the biodegradable polymer BES, compared with the durable polymer SES, was related to a significant reduction in very late ST (>1 year) and associated composite clinical outcomes. (Limus Eluted From A Durable Versus ERodable Stent Coating [LEADERS] trial; NCT00389220).

Serruys PW ，Farooq V ，Kalesan B ，de Vries T ，Buszman P ，Linke A ，Ischinger T ，Klauss V ，Eberli F ，Wijns W ，Morice MC ，Di Mario C ，Corti R ，Antoni D ，Sohn HY ，Eerdmans P ，Rademaker-Havinga T ，van Es GA ，Meier B ，Jüni P ，Windecker S ... -  《-》

Is Bare-Metal Stent Implantation Still Justifiable in High Bleeding Risk Patients Undergoing Percutaneous Coronary Intervention?: A Pre-Specified Analysis From the ZEUS Trial.

This study sought to investigate the ischemic and bleeding outcomes of patients fulfilling high bleeding risk (HBR) criteria who were randomized to zotarolimus-eluting Endeavor Sprint stent (E-ZES) or bare-metal stent (BMS) implantation followed by an abbreviated dual antiplatelet therapy (DAPT) duration for stable or unstable coronary artery disease. DES instead of BMS use remains controversial in HBR patients, in whom long-term DAPT poses safety concerns. The ZEUS (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates) is a multinational, randomized single-blinded trial that randomized among others, in a stratified manner, 828 patients fulfilling pre-defined clinical or biochemical HBR criteria-including advanced age, indication to oral anticoagulants or other pro-hemorrhagic medications, history of bleeding and known anemia-to receive E-ZES or BMS followed by a protocol-mandated 30-day DAPT regimen. The primary endpoint of the study was the 12-month major adverse cardiovascular event rate, consisting of death, myocardial infarction, or target vessel revascularization. Compared with patients without, those with 1 or more HBR criteria had worse outcomes, owing to higher ischemic and bleeding risks. Among HBR patients, major adverse cardiovascular events occurred in 22.6% of the E-ZES and 29% of the BMS patients (hazard ratio: 0.75; 95% confidence interval: 0.57 to 0.98; p = 0.033), driven by lower myocardial infarction (3.5% vs. 10.4%; p < 0.001) and target vessel revascularization (5.9% vs. 11.4%; p = 0.005) rates in the E-ZES arm. The composite of definite or probable stent thrombosis was significantly reduced in E-ZES recipients, whereas bleeding events did not differ between stent groups. Among HBR patients with stable or unstable coronary artery disease, E-ZES implantation provides superior efficacy and safety as compared with conventional BMS. (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates [ZEUS]; NCT01385319).

Ariotti S ，Adamo M ，Costa F ，Patialiakas A ，Briguori C ，Thury A ，Colangelo S ，Campo G ，Tebaldi M ，Ungi I ，Tondi S ，Roffi M ，Menozzi A ，de Cesare N ，Garbo R ，Meliga E ，Testa L ，Gabriel HM ，Ferlini M ，Vranckx P ，Valgimigli M ，ZEUS 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 ... -  《-》