Brazilian Clinical Research Institute, São Paulo, Brazil.
Duke Clinical Research Institute, Durham, North Carolina.
JAMA Cardiol. 2018 Nov 1;3(11):1113-1118. doi: 10.1001/jamacardio.2018.3408.
Loading doses of atorvastatin did not show reduction on clinical outcomes in the overall population of patients with acute coronary syndrome (ACS) enrolled in the Statins Evaluation in Coronary Procedures and Revascularization (SECURE-PCI) trial, but a potential benefit was identified in patients who subsequently underwent percutaneous coronary intervention (PCI).
To determine whether periprocedural loading doses of atorvastatin are associated with decreased 30-day major adverse cardiovascular events (MACE) in patients with ACS undergoing PCI according to type of ACS and timing of atorvastatin administration before PCI.
DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of a multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites that enrolled 4191 patients with ACS intended to be treated with PCI between April 18, 2012, and October 06, 2017.
Patients were randomized to 2 loading doses of 80 mg of atorvastatin or matching placebo before and 24 hours after a planned PCI. By protocol, all patients (regardless of treatment group) received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication.
The primary outcome was MACE through 30 days, composed by all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization. Cox regression models adjusting for key baseline characteristics were used to assess the association between atorvastatin and MACE in patients undergoing PCI.
From the overall trial population, 2710 (64.7%) underwent PCI (650 women [24.0%]; mean [SD] age, 62 [11.3] years). Loading atorvastatin was associated with reduced MACE at 30 days by 28% in the PCI group (adjusted hazard ratio [HR], 0.72; 95% CI 0.54-0.97; P = .03). Loading dose of atorvastatin was administered less than 12 hours before PCI in 2548 patients (95.3%) (45.1% < 2 hours and 54.3% between 2 and 12 hours). There was no significant interaction between treatment effect and timing of study drug administration. The treatment effect of loading atorvastatin was more pronounced in patients with ST-segment elevation myocardial infarction than in patients with non-ST-segment elevation ACS (adjusted HR, 0.59; 95% CI, 0.38-0.92; P = .02; HR, 0.85; 95% CI, 0.58-1.27; P = .43, respectively).
In patients with ACS undergoing PCI, periprocedural loading doses of atorvastatin appeared to reduce the rate of MACE at 30 days, most clearly in patients with ST-segment elevation myocardial infarction. This beneficial effect seemed to be preserved and consistent, irrespective of the timing of atorvastatin administration, including within 2 hours before PCI.
clinicaltrials.gov Identifier: NCT01448642.
在急性冠状动脉综合征（ACS）患者的总体人群中，阿托伐他汀的负荷剂量并未显示在 Statins Evaluation in Coronary Procedures and Revascularization（SECURE-PCI）试验中降低临床结局，但在随后接受经皮冠状动脉介入治疗（PCI）的患者中发现了潜在益处。
确定在接受 PCI 的 ACS 患者中，阿托伐他汀的围手术期负荷剂量是否与 30 天内主要不良心血管事件（MACE）的减少相关，具体取决于 ACS 的类型和 PCI 前阿托伐他汀给药的时间。
设计、设置和参与者：这是一项在 53 个地点进行的多中心、双盲、安慰剂对照、随机临床试验的二次分析，该试验纳入了 4191 名计划接受 PCI 治疗的 ACS 患者，招募时间为 2012 年 4 月 18 日至 2017 年 10 月 6 日。
患者被随机分为两组，分别在计划 PCI 前和 24 小时内接受 80mg 阿托伐他汀或匹配的安慰剂各 2 次负荷剂量。根据方案，所有患者（无论治疗组如何）在第二次研究药物剂量后 24 小时开始接受 30 天的 40mg 阿托伐他汀治疗。
主要结局是 30 天内的 MACE，包括全因死亡率、心肌梗死、卒中和非计划冠状动脉血运重建。使用调整关键基线特征的 Cox 回归模型来评估 PCI 患者中阿托伐他汀与 MACE 之间的关联。
在整个试验人群中，2710 人（64.7%）接受了 PCI（650 名女性[24.0%]；平均[标准差]年龄 62[11.3]岁）。在 PCI 组中，阿托伐他汀负荷剂量与 30 天内 MACE 降低 28%相关（调整后的危险比[HR]，0.72；95%CI，0.54-0.97；P=0.03）。在 2548 名患者（95.3%）中，阿托伐他汀负荷剂量在 PCI 前不到 12 小时内给药（45.1%<2 小时，54.3%在 2 至 12 小时之间）。治疗效果与研究药物给药时间之间没有显著的相互作用。在 ST 段抬高型心肌梗死患者中，阿托伐他汀负荷治疗的效果比非 ST 段抬高型 ACS 患者更为明显（调整后的 HR，0.59；95%CI，0.38-0.92；P=0.02；HR，0.85；95%CI，0.58-1.27；P=0.43）。
在接受 PCI 的 ACS 患者中，围手术期阿托伐他汀负荷剂量似乎降低了 30 天内的 MACE 发生率，在 ST 段抬高型心肌梗死患者中效果更为明显。这种有益的效果似乎是一致的，并且不受阿托伐他汀给药时间的影响，包括在 PCI 前 2 小时内。
clinicaltrials.gov 标识符：NCT01448642。
