Abstract

Aim

Patients with diabetes mellitus are at high risk of adverse events after percutaneous revascularization, with no differences in outcomes between most contemporary drug-eluting stents. The Cre8 EVO stent releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, and has shown clinical benefits in diabetes. We aimed to compare Cre8 EVO stents to Resolute Onyx stents (a contemporary polymer-based zotarolimus-eluting stent) in patients with diabetes.

Methods and results

We did an investigator-initiated, randomized, controlled, assessor-blinded trial at 23 sites in Spain. Eligible patients had diabetes and required percutaneous coronary intervention. A total of 1175 patients were randomly assigned (1:1) to receive Cre8 EVO or Resolute Onyx stents. The primary endpoint was target-lesion failure, defined as a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularization at 1-year follow-up. The trial had a non-inferiority design with a 4% margin for the primary endpoint. A superiority analysis was planned if non-inferiority was confirmed. There were 106 primary events, 42 (7.2%) in the Cre8 EVO group and 64 (10.9%) in the Resolute Onyx group [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.44 to 0.96; p_{non-inferiority} <0.001; p_superiority = 0.030]. Among the secondary endpoints, Cre8 EVO stents had significantly lower rate than Resolute Onyx stents of target-vessel failure (7.5% vs 11.1%, HR 0.67, 95% CI 0.46 to 0.99; p = 0.042). Probable or definite stent thrombosis and all-cause death were not significantly different between groups.

Conclusions

In patients with diabetes, Cre8 EVO stents were non-inferior to Resolute Onyx stents with regard to target-lesion failure composite outcome. An exploratory analysis for superiority at 1 year suggests that the Cre8 EVO stents might be superior to Resolute Onyx stents with regard to the same outcome.

Clinical trial registration

ClinicalTrials.gov: NCT03321032.

中文翻译：

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Amphilimus 与佐他莫司洗脱支架治疗糖尿病和冠状动脉疾病患者的对比（SUGAR 试验）

 抽象的

 目的

糖尿病患者在经皮血运重建后发生不良事件的风险很高，而大多数当代药物洗脱支架的结果没有差异。 Cre8 EVO 支架从激光挖井中释放出西罗莫司制剂和两亲性载体，并已显示出治疗糖尿病的临床益处。我们的目的是在糖尿病患者中比较 Cre8 EVO 支架与 Resolute Onyx 支架（一种当代聚合物佐他莫司洗脱支架）。

 方法和结果

我们在西班牙 23 个地点进行了一项由研究者发起、随机、对照、评估者盲法的试验。符合条件的患者患有糖尿病并需要经皮冠状动脉介入治疗。共有 1175 名患者被随机分配 (1:1) 接受 Cre8 EVO 或 Resolute Onyx 支架。主要终点是靶病灶失败，定义为心源性死亡、靶血管心肌梗死和一年随访时临床指示的靶病灶血运重建的复合终点。该试验采用非劣效性设计，主要终点裕度为 4%。如果确认非劣效性，则计划进行优效性分析。主要事件有 106 起，其中 Cre8 EVO 组有 42 起（7.2%），Resolute Onyx 组有 64 起（10.9%）[风险比 (HR) 0.65，95% 置信区间 (CI) 0.44 至 0.96； p_非劣效<0.001； p_优势= 0.030]。在次要终点中，Cre8 EVO 支架的靶血管失败率显着低于 Resolute Onyx 支架（7.5% vs 11.1%，HR 0.67，95% CI 0.46 至 0.99；p = 0.042）。可能或明确的支架血栓形成和全因死亡在各组之间没有显着差异。

 结论

在糖尿病患者中，就目标病变失败综合结果而言，Cre8 EVO 支架并不劣于 Resolute Onyx 支架。 1 年优越性的探索性分析表明，就相同结果而言，Cre8 EVO 支架可能优于 Resolute Onyx 支架。

临床试验注册

ClinicalTrials.gov：NCT03321032。