Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, Netherlands; Department of Health Technology and Services Research, MIRA-Institute of Technical Medicine and Biomedical Technology, University of Twente, Enschede, Netherlands.
Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, Netherlands.
Lancet. 2016 Nov 26;388(10060):2607-2617. doi: 10.1016/S0140-6736(16)31920-1. Epub 2016 Oct 30.
In patients with coronary artery disease, treated with durable polymer-coated drug-eluting stents, the life-long presence of the polymer might delay arterial healing. Novel very thin strut biodegradable polymer stents, which leave only a bare metal stent after polymer resorption, might improve long-term outcome. We investigated in allcomers the safety and efficacy of three stents eluting either everolimus, sirolimus, or zotarolimus, often clinically used but never compared, of which the biodegradable polymer everolimus-eluting stent was never before assessed in allcomers.
The large-scale, investigator-initiated, multicentre, assessor and patient blinded, three-arm, randomised, BIO-RESORT non-inferiority trial was done at four clinical sites in the Netherlands. All-comer patients were aged 18 years or older, capable of providing informed consent, and required a percutaneous coronary intervention with drug-eluting stent implantation according to clinical guidelines or the operators' judgment. Exclusion criteria were: participation in another randomised drug or device study before reaching the primary endpoint of that study; planned surgery necessitating interruption of dual antiplatelet therapy within the first 6 months; known intolerance to components of the investigational product or medication required; uncertainty about the adherence to follow-up procedures or an assumed life expectancy of less than 1 year; or known pregnancy. Web-based computer-generated allocation sequences randomly assigned patients (1:1:1) to treatment with very thin strut biodegradable polymer everolimus-eluting or sirolimus-eluting stents (which differ substantially in type, amount, distribution, and resorption speed of their respective coating), or thin strut durable polymer zotarolimus-eluting stents. The primary endpoint was a composite of safety (cardiac death or target vessel-related myocardial infarction) and efficacy (target vessel revascularisation) at 12 months of follow up with a very thin strut biodegradable polymer of either everolimus-eluting or sirolimus-eluting stents, compared with durable polymer zotarolimus-eluting stents, analysed by intention to treat (non-inferiority margin 3·5%). This trial was registered with ClinicalTrials.gov, number NCT01674803.
From Dec 21, 2012, to Aug 24, 2015, 3514 patients were enrolled and analysed, of whom 2449 (70%) had acute coronary syndromes, which included 1073 (31%) ST-elevation myocardial infarctions. 12 month follow-up of 3490 (99%) patients (three lost to follow-up; 21 withdrawals) was available. The primary endpoint was met by 55 (5%) of 1172 patients assigned to everolimus-eluting stents, 55 (5%) of 1169 assigned to sirolimus-eluting stents and 63 (5%) of 1173 assigned to zotarolimus-eluting stents. Non-inferiority of the everolimus-eluting stents and sirolimus-eluting stents compared with zotarolimus-eluting stents was confirmed (both -0·7% absolute risk difference, 95% CI -2·4 to 1·1; upper limit of one sided 95% CI 0·8%, p<0·0001). Definite stent thrombosis (defined by the Academic Research Consortium) occurred in four (0·3%) of 1172 patients who were allocated to everolimus-eluting stents, four (0·3%) of 1169 patients who were allocated to sirolimus-eluting stents, and three (0·3%) of 1173 patients who were allocated to zotarolimus-eluting stents (log-rank p=0·70 for both comparisons with zotarolimus-eluting stents).
At 12 month follow-up, both very thin strut drug-eluting stents with dissimilar biodegradable polymer coatings (eluting either everolimus or sirolimus) were non-inferior to the durable polymer stent (eluting zotarolimus) in treating allcomers with a high proportion of patients with acute coronary syndromes. The absence of a loss of 1 year safety and efficacy with the use of these two biodegradable polymer-coated stents is a prerequisite before assessing their potential longer-term benefits.
Biotronik, Boston Scientific, and Medtronic.
在接受持久聚合物涂层药物洗脱支架治疗的冠状动脉疾病患者中，聚合物的终身存在可能会延迟动脉愈合。新型极薄支架生物可吸收聚合物支架，在聚合物吸收后仅留下裸金属支架，可能会改善长期预后。我们在所有患者中研究了经常临床使用但从未比较过的三种支架的安全性和疗效，其中生物可吸收聚合物依维莫司洗脱支架从未在所有患者中进行过评估。
这项大规模、由研究者发起的、多中心、评估者和患者双盲、三臂、随机、BIO-RESORT 非劣效性试验在荷兰的四个临床地点进行。所有患者年龄均在 18 岁或以上，能够提供知情同意，并根据临床指南或操作者的判断需要经皮冠状动脉介入治疗并植入药物洗脱支架。排除标准为：在该研究的主要终点前已参与另一项随机药物或器械研究；计划手术需要在 6 个月内中断双联抗血小板治疗；已知对研究产品或药物有成分不耐受；对随访程序的依从性存在不确定性或假定预期寿命不足 1 年；或已知怀孕。基于网络的计算机生成的分配序列将患者（1:1:1）随机分配至极薄支架生物可吸收聚合物依维莫司洗脱支架或西罗莫司洗脱支架（这两种支架在类型、数量、分布和吸收速度方面存在显著差异）或薄支架持久聚合物佐他莫司洗脱支架治疗。主要终点是在 12 个月的随访中，极薄支架生物可吸收聚合物依维莫司洗脱支架或西罗莫司洗脱支架与持久聚合物佐他莫司洗脱支架相比的安全性（心源性死亡或靶血管相关心肌梗死）和疗效（靶血管血运重建）的复合终点，分析采用意向治疗（非劣效性边界 3.5%）。该试验在 ClinicalTrials.gov 上注册，编号为 NCT01674803。
从 2012 年 12 月 21 日至 2015 年 8 月 24 日，共纳入 3514 例患者进行分析，其中 2449 例（70%）为急性冠状动脉综合征，包括 1073 例（31%）ST 段抬高型心肌梗死。3490 例（99%）患者（3 例失访；21 例退出）获得 12 个月随访。1172 例接受依维莫司洗脱支架治疗的患者中有 55 例（5%）、1169 例接受西罗莫司洗脱支架治疗的患者中有 55 例（5%）和 1173 例接受佐他莫司洗脱支架治疗的患者中有 63 例（5%）达到主要终点。依维莫司洗脱支架和西罗莫司洗脱支架与佐他莫司洗脱支架相比的非劣效性得到确认（绝对风险差异分别为-0.7%，95%CI-2.4 至 1.1；单侧 95%CI 上限 0.8%，p<0.0001）。在接受依维莫司洗脱支架治疗的 1172 例患者中，有 4 例（0.3%）发生明确的支架血栓形成（定义为学术研究联合会），在接受西罗莫司洗脱支架治疗的 1169 例患者中有 4 例（0.3%），在接受佐他莫司洗脱支架治疗的 1173 例患者中有 3 例（0.3%）（两者与佐他莫司洗脱支架相比的对数秩检验 p=0.70）。
在 12 个月的随访中，两种极薄支架药物洗脱支架（分别洗脱依维莫司或西罗莫司）在治疗高比例急性冠状动脉综合征患者方面均不劣于持久聚合物支架（洗脱佐他莫司）。在评估这两种生物可吸收聚合物涂层支架的潜在长期获益之前，必须先确认使用这两种支架在 1 年内不会丧失安全性和疗效。
百多力、波士顿科学和美敦力。
