Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
China National Clinical Research Center for Neurological Diseases, Beijing, China.
JAMA Neurol. 2024 Jul 1;81(7):741-751. doi: 10.1001/jamaneurol.2024.1433.
Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic stroke or transient ischemic attack (TIA) from atherosclerosis.
To estimate whether immediate-intensive statin therapy is safe and can lower the risk of recurrent stroke compared with delayed-intensive statin in patients with acute mild ischemic stroke or high-risk TIA from atherosclerosis.
DESIGN, SETTING, AND PARTICIPANTS: The Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-blind, placebo-controlled, 2 × 2 factorial, randomized clinical trial enrolled patients from September 2018 to October 2022. The trial was conducted at 222 hospitals in China. Patients aged 35 to 80 years with mild ischemic stroke or high-risk TIA of presumed atherosclerosis within 72 hours of symptom onset were assessed.
Patients were randomly assigned to receive immediate-intensive atorvastatin (80 mg daily on days 1-21; 40 mg daily on days 22-90) or 3-day delayed treatment (placebo for days 1-3, followed by placebo and atorvastatin, 40 mg daily on days 4-21, and then atorvastatin, 40 mg daily on days 22-90).
The primary efficacy outcome was new stroke within 90 days, and a secondary efficacy outcome was poor functional outcome. Moderate to severe bleeding was the primary safety outcome.
A total of 11 431 patients were assessed for eligibility, and 6100 patients (median [IQR] age, 65 [57-71] years; 3915 men [64.2%]) were enrolled, with 3050 assigned to each treatment group. Within 90 days, new stroke occurred in 245 patients (8.1%) in the immediate-intensive statin group and 256 patients (8.4%) in the delayed group (hazard ratio, 0.95; 95% CI, 0.80-1.13). Poor functional outcome occurred in 299 patients (9.8%) and 348 patients (11.4%) in the immediate-intensive and delayed-intensive statin groups, respectively (odds ratio, 0.83; 95% CI, 0.71-0.98). Moderate to severe bleeding occurred in 23 of 3050 patients (0.8%) and 17 of 3050 patients (0.6%), in the immediate-intensive and delayed-intensive statin groups, respectively.
Immediate-intensive statin initiated within 72 hours did not reduce the risk of stroke within 90 days and may be associated with improved functional outcomes without significant difference in moderate to severe bleeding, compared with 3-day delayed-intensive statin in Chinese patients with acute mild ischemic stroke or TIA from atherosclerosis.
ClinicalTrials.gov Identifier: NCT03635749.
重要性：对于因动脉粥样硬化导致的急性轻度缺血性卒中和短暂性脑缺血发作（TIA）患者，强化他汀类药物和延迟强化他汀类药物在二级预防和神经保护方面的比较有限。
目的：评估与延迟强化他汀类药物相比，急性轻度缺血性卒中和高风险 TIA 患者立即强化他汀类药物治疗是否安全，是否可以降低复发性卒中的风险。
设计、设置和参与者：强化他汀类药物和抗血小板治疗高危颅内或颅外动脉粥样硬化（INSPIRES）试验是一项双盲、安慰剂对照、2×2 析因、随机临床试验，纳入了 2018 年 9 月至 2022 年 10 月期间发病 72 小时内的轻度缺血性卒中和高风险 TIA 的假定动脉粥样硬化患者。该试验在中国的 222 家医院进行。评估年龄在 35 至 80 岁之间、有轻度缺血性卒中和高风险 TIA 的患者。
干预措施：患者被随机分配接受立即强化阿托伐他汀（第 1-21 天每天 80 毫克；第 22-90 天每天 40 毫克）或 3 天延迟治疗（第 1-3 天安慰剂，然后安慰剂和阿托伐他汀，第 4-21 天每天 40 毫克，然后第 22-90 天每天 40 毫克）。
主要结局和测量指标：主要疗效结局是 90 天内新发卒中，次要疗效结局是不良功能结局。中度至重度出血是主要安全性结局。
结果：共有 11431 名患者符合入选标准，其中 6100 名患者（中位数[IQR]年龄，65[57-71]岁；3915 名男性[64.2%]）被纳入研究，每组 3050 名。在 90 天内，立即强化他汀组有 245 名（8.1%）患者发生新卒中，延迟组有 256 名（8.4%）患者发生新卒中（风险比，0.95；95%CI，0.80-1.13）。立即强化他汀组和延迟强化他汀组分别有 299 名（9.8%）和 348 名（11.4%）患者发生不良功能结局（优势比，0.83；95%CI，0.71-0.98）。立即强化他汀组有 23 名（0.8%）患者和延迟强化他汀组有 17 名（0.6%）患者发生中度至重度出血。
结论和相关性：与 3 天延迟强化他汀类药物相比，在中国急性轻度缺血性卒中和 TIA 患者中，发病 72 小时内开始的立即强化他汀类药物治疗并未降低 90 天内卒中风险，且可能改善功能结局，而中度至重度出血无显著差异。
试验注册：ClinicalTrials.gov 标识符：NCT03635749。
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