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 ... -  《-》

Two-year outcomes after first- or second-generation drug-eluting or bare-metal stent implantation in all-comer patients undergoing percutaneous coronary intervention: a pre-specified analysis from the PRODIGY study (PROlonging Dual Antiplatelet Treatment

This study sought to assess device-specific outcomes after implantation of bare-metal stents (BMS), zotarolimus-eluting Endeavor Sprint stents (ZES-S), paclitaxel-eluting stents (PES), or everolimus-eluting stents (EES) (Medtronic Cardiovascular, Santa Rosa, California) in all-comer patients undergoing percutaneous coronary intervention. Few studies have directly compared second-generation drug-eluting stents with each other or with BMS. We randomized 2,013 patients to BMS, ZES-S, PES, or EES implantation. At 30 days, each stent group received up to 6 or 24 months of clopidogrel therapy. The key efficacy endpoint was the 2-year major adverse cardiac event (MACE) including any death, myocardial infarction, or target vessel revascularization, whereas the cumulative rate of definite or probable stent thrombosis (ST) was the key safety endpoint. Clinical follow-up at 2 years was complete for 99.7% of patients. The MACE rate was lowest in EES (19.2%; 95% confidence interval [CI]: 16.0 to 22.8), highest in BMS (32.1%; 95% CI: 28.1 to 36.3), and intermediate in PES (26.2%; 95% CI: 22.5 to 30.2) and ZES-S (27.8%; 95% CI: 24.1 to 31.9) groups (chi-square test = 18.9, p = 0.00029). The 2-year incidence of ST in the EES group (1%; 95% CI: 0.4 to 2.2) was similar to that in the ZES-S group (1.4%; 95% CI: 0.7 to 2.8), whereas it was lower compared with the PES (4.6%, 95% CI: 3.1 to 6.8) and BMS (3.6%; 95% CI: 2.4 to 5.6) groups (chi-square = 16.9; p = 0.0001). Our study shows that cumulative MACE rate, encompassing both safety and efficacy endpoints, was lowest for EES, highest for BMS, and intermediate for PES and ZES-S groups. EES outperformed BMS also with respect to the safety endpoints with regard to definite or probable and definite, probable, or possible ST. (PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY [PRODIGY]; NCT00611286).

Valgimigli M ，Tebaldi M ，Borghesi M ，Vranckx P ，Campo G ，Tumscitz C ，Cangiano E ，Minarelli M ，Scalone A ，Cavazza C ，Marchesini J ，Parrinello G ，PRODIGY Investigators ... -  《-》

Zotarolimus-eluting versus bare-metal stents in uncertain drug-eluting stent candidates.

The use of drug-eluting stents (DES) in patients at high risk of bleeding or thrombosis has not been prospectively studied; limited data are available in patients who have a low restenosis risk. This study sought to compare a hydrophilic polymer-based, second-generation zotarolimus-eluting stent (ZES) with a unique drug fast-release profile versus bare-metal stents (BMS) under similar durations of dual-antiplatelet therapy (DAPT). We randomly assigned 1,606 patients with stable or unstable symptoms, and who on the basis of thrombotic bleeding or restenosis risk criteria, qualified as uncertain candidates for DES, to receive ZES or BMS. DAPT duration was on the basis of patient characteristics, rather than stent characteristics, and allowed for a personalized 1-month dual antiplatelet regimen. The primary endpoint was the risk of 1-year major adverse cardiovascular events (MACE), which included death, myocardial infarction (MI), or target vessel revascularization (TVR). Median DAPT duration was 32 days (interquartile range [IQR]: 30 to 180 days) and did not differ between the groups. In the ZES group, 140 patients (17.5%) reached the primary endpoint, compared with 178 patients (22.1%) in the BMS group (hazard ratio: 0.76; 95% confidence interval: 0.61 to 0.95; p = 0.011) as a result of lower MI (2.9% vs. 8.1%; p < 0.001) and TVR rates (5.9% vs.10.7%; p = 0.001) in the ZES group. Definite or probable stent thrombosis was also significantly reduced in ZES recipients (2.0% vs. 4.1%; p = 0.019). Compared with BMS, DES implantation using a stent with a biocompatible polymer and fast drug-eluting characteristics, combined with an abbreviated, tailored DAPT regimen, resulted in a lower risk of 1-year MACE in uncertain candidates for DES implantation. (Zotarolimus-eluting Endeavor Sprint Stent in Uncertain DES Candidates [ZEUS] Study; NCT01385319).

Valgimigli M ，Patialiakas A ，Thury A ，McFadden E ，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 ，Airoldi F ，Ferlini M ，Liistro F ，Dellavalle A ，Vranckx P ，Briguori C ，ZEUS Investigators ... -  《-》

Randomized comparison of Zotarolimus-Eluting Endeavor Sprint versus bare-metal stent implantation in uncertain drug-eluting stent candidates: rationale, design, and characterization of the patient population for the Zotarolimus-eluting Endeavor Sprint ste

The use of drug-eluting stent (DES) instead of bare-metal stent (BMS) in patients at high stent thrombosis or bleeding risk as well as in those at low restenosis risk (ie, uncertain DES candidates) remains a matter of debate. Zotarolimus-Eluting Endeavor Sprint stent (E-ZES) (Santa Rosa, CA) is a hydrophilic polymer-based second-generation device with unique drug fast-release profile, which may allow for a shorter dual antiplatelet therapy (DAPT) duration without safety concerns. The primary objective is to assess whether E-ZES implantation followed by a shorter than currently recommended course of DAPT will decrease the incidence of 12-month major adverse cardiovascular events as compared with BMS in undefined DES recipients. Actual duration of DAPT regimen will be dictated by patients' characteristics and not by stent type and, as such, can be as short as 30 days after intervention in both stent groups. The ZEUS study is an open-label randomized clinical trial conducted at 20 clinical sites in Italy, Switzerland, Portugal, and Hungary. With 1,600 individuals, this study will have 85% power to detect a 33% difference in the primary end point consisting of the composite of death, nonfatal myocardial infarction, or target vessel revascularization. The ZEUS trial aims to assess whether the use of E-ZES, followed by a DAPT duration regimen based on patients' characteristics and not by stent type, is superior to conventional BMS implantation in undefined DES recipients who qualify for the presence of high thrombosis, bleeding, or low restenosis risk criteria.

Valgimigli M ，Patialiakas A ，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 ，Airoldi F ，Ferlini M ，Liistro F ，Dellavalle A ，Vranckx P ，Briguori C ... -  《-》

Final 5-year outcomes from the Endeavor zotarolimus-eluting stent clinical trial program: comparison of safety and efficacy with first-generation drug-eluting and bare-metal stents.

The aim of this study was to evaluate late safety and efficacy outcomes among patients enrolled in clinical trials comparing Endeavor zotarolimus-eluting stents (E-ZES) (Medtronic, Inc., Santa Rosa, California) with first-generation drug-eluting stents (DES) and bare-metal stents (BMS). Despite demonstration of higher angiographic luminal loss and restenosis with E-ZES compared with alternative DES, whether differences in these early angiographic measures translate into more disparate late clinical events is uncertain. Among 3,616 patients undergoing percutaneous coronary revascularization in 5 registration trials, late safety and efficacy events were compared between E-ZES (n = 2,132) versus sirolimus- or paclitaxel-eluting stents (n = 888) or BMS (n = 596). Compared with a parallel cohort of patients treated with first-generation DES and BMS, 5-year rates of cardiac death/myocardial infarction (MI) (5.8% vs. 8.8% DES, p = 0.003; vs. 8.4% BMS, p = 0.02) and major adverse cardiac events (16.1% vs. 20.6% DES, p = 0.009; vs. 24.6% BMS, p < 0.001) were significantly lower with E-ZES. The E-ZES was associated with significantly lower target lesion revascularization (TLR) compared with BMS (7.4% vs. 16.3%, p < 0.001) but similar to comparator DES (7.4% vs. 8.1%, p = 0.63). Despite higher TLR in the first year with E-ZES compared with DES, between 1- and 5-year follow-up, rates of cardiac death/MI, TLR, and definite/probable stent thrombosis were significantly lower with E-ZES. Over 5 years, significant differences in cardiac death/MI and composite endpoints favored treatment with E-ZES over comparator BMS and DES. Rates of clinical restenosis and safety events, including stent thrombosis beyond the first year of revascularization, remain stable with E-ZES, leading to significant differences compared with first-generation DES.

Kandzari DE ，Leon MB ，Meredith I ，Fajadet J ，Wijns W ，Mauri L ... -  《-》