Nikolsky Eugenia, Lansky Alexandra J, Sudhir Krishnankutty, Doostzadeh Julie, Cutlip Donald E, Piana Robert, Su Xiaolu, White Roseann, Simonton Charles A, Stone Gregg W
Columbia University Medical Center and The Cardiovascular Research Foundation, New York, NY 10022, USA.
Am Heart J. 2009 Oct;158(4):520-526.e2. doi: 10.1016/j.ahj.2009.07.025. Epub 2009 Aug 26.
In the 300-patient SPIRIT II and 1002-patient SPIRIT III randomized trials, the everolimus-eluting stent (EES) compared to the paclitaxel-eluting stent (PES) resulted in reduced angiographic late loss (a primary end point in both trials), noninferior rates of 9-month target vessel failure (a primary end point in SPIRIT III), and reduced rates of target lesion revascularization and major adverse cardiac events (secondary end points). However, neither trial was powered for superiority for clinical end points, and the routine performance of angiographic follow-up may have artificially exaggerated the absolute benefits of EES. The relative efficacy of these 2 stents in patients with diabetes mellitus also remains controversial. We therefore designed a large-scale randomized trial without angiographic follow-up to further assess the differences between these 2 stent platforms.
SPIRIT IV is an ongoing prospective, active-controlled, single-blinded, multicenter clinical trial in which 3690 patients with native coronary artery disease have been randomized 2:1 to EES versus PES. Patients with up to 3 de novo native coronary artery lesions (maximum 2 lesions per epicardial vessel) with length <or=28 mm and reference vessel diameter >or=2.5 to <or=4.25 mm were enrolled at 66 US clinical sites. Clinical follow-up at 30, 180, and 270 days; 1 year; and then yearly for up to 5 years is underway. The primary end point is the rate of ischemia-driven target lesion failure at 1 year, a composite measure of safety and efficacy consisting of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization, with the trial powered for sequential noninferiority and superiority testing.
SPIRIT IV is the largest randomized comparison of 2 DES with completed enrollment. The absence of routine angiographic follow-up will allow an accurate assessment of the absolute differences in the clinical safety and efficacy profile between these devices. The magnitude of the study will also permit significant insights to be gained into the relative performance of the 2 stents in important subgroups, including patients with diabetes mellitus.
在纳入300例患者的SPIRIT II试验和纳入1002例患者的SPIRIT III随机试验中，与紫杉醇洗脱支架（PES）相比，依维莫司洗脱支架（EES）可减少血管造影晚期管腔丢失（两项试验的主要终点），9个月靶血管失败率（SPIRIT III的主要终点）不劣于紫杉醇洗脱支架，且靶病变血运重建率和主要不良心脏事件（次要终点）降低。然而，两项试验均未针对临床终点进行优效性检验，且血管造影随访的常规操作可能人为夸大了EES的绝对获益。这两种支架在糖尿病患者中的相对疗效也仍存在争议。因此，我们设计了一项不进行血管造影随访的大规模随机试验，以进一步评估这两种支架平台之间的差异。
SPIRIT IV是一项正在进行的前瞻性、活性对照、单盲、多中心临床试验，3690例原发性冠状动脉疾病患者按2:1随机分组，分别接受EES和PES治疗。入选患者有多达3处原发性冠状动脉新发病变（每支心外膜血管最多2处病变），病变长度≤28 mm，参考血管直径≥2.5至≤4.25 mm，来自美国66个临床中心。目前正在进行30天、180天、270天、1年的临床随访，之后每年随访一次，最长随访5年。主要终点是1年时缺血驱动的靶病变失败率，这是一项安全性和疗效的综合指标，包括心源性死亡、靶血管心肌梗死或缺血驱动的靶病变血运重建，该试验旨在进行序贯非劣效性和优效性检验。
SPIRIT IV是已完成入组的两种药物洗脱支架最大规模的随机对照试验。不进行常规血管造影随访将能够准确评估这些器械在临床安全性和疗效方面的绝对差异。该研究的规模还将有助于深入了解这两种支架在包括糖尿病患者在内的重要亚组中的相对性能。
