Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands2Health Technology and Services Research, MIRA-Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands.
Department of Cardiology, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands.
JAMA Cardiol. 2017 Mar 1;2(3):268-276. doi: 10.1001/jamacardio.2016.5190.
Long-term follow-up after a clinical trial of 2 often-used, newer-generation drug-eluting stents (DESs) in a broad patient population is of interest. Comprehensive long-term outcome of eligible nonenrolled patients has never been reported.
To assess 5-year safety and efficacy of 2 newer-generation DESs in randomized participants with non-ST-elevation acute coronary syndromes or stable angina and to evaluate long-term outcomes of nonenrolled eligible patients treated with the same DESs.
DESIGN, SETTING, AND PARTICIPANTS: The TWENTE (Real-World Endeavor Resolute vs Xience V Drug-Eluting Stent Study in Twente) trial is an investigator-initiated, patient-blinded, randomized, comparative DES trial that enrolled patients from June 18, 2008, to August 26, 2010. Most patients had non-ST-elevation acute coronary syndromes and complex lesions. Of all 1709 eligible patients, 1391 (81.4%) were treated in the TWENTE trial with zotarolimus-eluting (ZES, n = 697) or everolimus-eluting (EES, n = 694) cobalt-chromium stents. The remaining 318 eligible patients (18.6%) were not enrolled but underwent nonrandomized treatment with the same DESs. Data were analyzed from August 26, 2015, to October 11, 2016. Event rates (percentages) were derived from log-rank analysis and may differ from straightforward calculation (nominator/denominator). The 5-year follow-up of the TWENTE participants was prespecified in the trial protocol; that of the nonenrolled participants was ad hoc.
Target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization.
Of 1709 eligible participants, 1233 (72.1%) were men, 476 (27.9%) were women, and mean (SD) age was 64.6 (10.6) years. Among the 1370 of 1391 TWENTE trial participants (98.5% follow-up), TVF was similar between those in the ZES (16.1%) and EES (18.1%) groups (P = .36). Stent thrombosis rates were low: definite (7 of 697 [1.0%] vs 4 of 694 [0.6%]; P = .37) and occurred after more than 1 year in 3 (0.4%) with ZES vs 4 (0.6%) with EES (P = .69). The 318 nonenrolled eligible patients (308 patients [96.9%] of whom were followed up) were older and had more advanced disease than trial participants. Their TVF rate was higher than that of trial participants (71 of 318 [23.3%] vs 233 of 1391 [17.1%]; P = .02), which partly reflects a difference in cardiac mortality (23 of 318 [7.7%] vs 60 of 1391 [4.5%]; P = .03). Similar 5-year rates were found for myocardial infarction (91 of 1391 [6.7%] vs 22 of 318 [7.2%]; P = .80) and target vessel revascularization (129 of 1391 [9.7%] vs 34 of 318 [11.4%]; P = .36) between trial participants and nonenrolled eligible patients. In all eligible patients (ie, trial participants plus nonenrolled eligible patients), the TVF rate was only slightly higher than in trial participants only (18.3% vs 17.1%).
Long-term outcome data from nonenrolled eligible patients support the validity of the TWENTE trial findings and present, with the trial, a strong case for the long-term safety and efficacy of the newer-generation DESs used.
clinicaltrials.gov Identifier: NCT01066650.
对两种常用的新一代药物洗脱支架（DES）在广泛的患者人群中的长期随访结果很感兴趣。从未报道过符合条件但未入组的患者的全面长期结局。
评估 2 种新型 DES 在非 ST 段抬高型急性冠状动脉综合征或稳定型心绞痛的随机参与者中的 5 年安全性和有效性，并评估使用相同 DES 治疗的非入组合格患者的长期结局。
设计、地点和参与者：TWENTE（真实世界 Endeavor Resolute 与 Xience V 药物洗脱支架在特温特的研究）试验是一项由研究者发起、患者设盲、随机、比较 DES 试验，于 2008 年 6 月 18 日至 2010 年 8 月 26 日招募患者。大多数患者患有非 ST 段抬高型急性冠状动脉综合征和复杂病变。在所有 1709 名合格患者中，1391 名（81.4%）在 TWENTE 试验中接受了佐他莫司洗脱支架（ZES，n=697）或依维莫司洗脱支架（EES，n=694）钴铬支架治疗。其余 318 名（18.6%）合格患者未入组，但接受了相同 DES 的非随机治疗。数据于 2015 年 8 月 26 日至 2016 年 10 月 11 日进行分析。事件发生率（百分比）来自对数秩分析，可能与直接计算结果不同（分子/分母）。TWENTE 参与者的 5 年随访是在试验方案中预先设定的，而非入组参与者的随访是临时设定的。
靶血管失败（TVF），是指心脏死亡、靶血管相关心肌梗死或靶血管血运重建的复合终点。
在 1709 名合格患者中，1233 名（72.1%）为男性，476 名（27.9%）为女性，平均（SD）年龄为 64.6（10.6）岁。在 1370 名 TWENTE 试验参与者中（98.5%的随访率），ZES 组（16.1%）和 EES 组（18.1%）的 TVF 相似（P=0.36）。支架血栓形成率较低：明确的（7/697[1.0%]与 4/694[0.6%]；P=0.37），3 例（0.4%）发生在 ZES 后超过 1 年，4 例（0.6%）发生在 EES（P=0.69）。318 名符合条件但未入组的患者（308 名患者[96.9%]接受了随访）年龄较大，且疾病较严重。他们的 TVF 发生率高于试验参与者（318 例中的 71 例[23.3%]与 1391 例中的 233 例[17.1%]；P=0.02），这在一定程度上反映了心脏死亡率的差异（318 例中的 23 例[7.7%]与 1391 例中的 60 例[4.5%]；P=0.03）。试验参与者和非入组合格患者的心肌梗死（1391 例中的 91 例[6.7%]与 318 例中的 22 例[7.2%]；P=0.80）和靶血管血运重建（1391 例中的 129 例[9.7%]与 318 例中的 34 例[11.4%]；P=0.36）的 5 年发生率相似。在所有合格患者（即试验参与者加非入组合格患者）中，TVF 发生率仅略高于仅试验参与者（18.3%比 17.1%）。
非入组合格患者的长期结局数据支持 TWENTE 试验结果的有效性，并提供了强有力的证据证明新型 DES 的长期安全性和有效性。
clinicaltrials.gov 标识符：NCT01066650。
