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Randomized Controlled Trial
. 2024 Jul 1;81(7):741-751.
doi: 10.1001/jamaneurol.2024.1433.

Immediate- or Delayed-Intensive Statin in Acute Cerebral Ischemia: The INSPIRES Randomized Clinical Trial

Ying Gao  1 , Lingling Jiang  2 , Yuesong Pan  1   2 , Weiqi Chen  1 , Jing Jing  1   2 , Chunjuan Wang  1   2 , S Claiborne Johnston  3 , Pierre Amarenco  4   5 , Philip M Bath  6 , Yingying Yang  1 , Tingting Wang  1 , Shangrong Han  1 , Xia Meng  1   2 , Jinxi Lin  2 , Xingquan Zhao  1   2 , Liping Liu  1   2 , Jinguo Zhao  7 , Ying Li  8 , Yingzhuo Zang  9 , Shuo Zhang  10 , Hongqin Yang  11 , Jianbo Yang  12 , Yuanwei Wang  13 , Dali Li  14 , Yanxia Wang  15 , Dongqi Liu  15 , Guangming Kang  16 , Yongjun Wang  1   2   17   18   19 , Yilong Wang  1   2   17   18   20   21   22 ; INSPIRES Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Immediate- or Delayed-Intensive Statin in Acute Cerebral Ischemia: The INSPIRES Randomized Clinical Trial

Ying Gao et al. JAMA Neurol. .

Abstract

Importance: 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.

Objective: 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.

Interventions: 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).

Main outcomes and measures: 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.

Results: 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.

Conclusions and relevance: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT03635749.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Johnston reported receiving advisory board/trial leadership fees from AstraZeneca, Johnson & Johnson, and BMS outside the submitted work. Dr Amarenco reported receiving grants from the French government, AstraZeneca, and Pfizer and speaker/advisory board fees from Novartis, Amgen, and Sanofi outside the submitted work. Dr Bath reported receiving advisory board fees from CoMind, Roche, and DiaMedica and nonfinancial support from Phagenesis (devices) outside the submitted work. Dr Yilong Wang reported receiving grants from Sanofi and Beijing Jialin Pharmaceuticals during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Enrollment and Randomization of Patients
Patients who were enrolled inappropriately or discontinued trial drug were included in the intention-to-treat analysis, as were patients who died of a cause other than stroke or were lost to follow-up. The ABCD2 score assess the risk of stroke on the basis of age, blood pressure, clinical features, duration of transient ischemic attack (TIA), and presence of diabetes (range, 0-7, higher scores indicating higher risk of stroke) ICH indicates intracerebral hemorrhage; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; SAH, subarachnoid hemorrhage.
Figure 2.
Figure 2.. Cumulative Probability of Stroke (Primary Efficacy Outcome) and Moderate to Severe Bleeding and Distribution of Modified Rankin Scale (mRS) Score
A, The probability of ischemic or hemorrhagic stroke. B, The probability of moderate to severe bleeding. C, The distribution of mRS score. HR indicates hazard ratio.
Figure 3.
Figure 3.. Hazard Ratio (HR) for the Stroke According to Prespecified Subgroups
The trial was not powered to allow definite conclusions based on the results of the subgroup analyses. Systolic blood pressure data were missing in 8 patients in the immediate statin group and 5 patients in the delayed statin group. Data on 50% or greater symptomatic stenosis were missing in 71 patients in the immediate statin group and 61 patients in the delayed statin group. NIHSS indicates National Institutes of Health Stroke Scale.
See this image and copyright information in PMC

References

    1. Shahjouei S, Sadighi A, Chaudhary D, et al. . A 5-decade analysis of incidence trends of ischemic stroke after transient ischemic attack: a systematic review and meta-analysis. JAMA Neurol. 2021;78(1):77-87. doi:10.1001/jamaneurol.2020.3627 - DOI - PMC - PubMed
    1. Park TH, Lee JK, Park MS, et al. . Neurologic deterioration in patients with acute ischemic stroke or transient ischemic attack. Neurology. 2020;95(16):e2178-e2191. doi:10.1212/WNL.0000000000010603 - DOI - PubMed
    1. Goldstein LB, Amarenco P, Zivin J, et al. ; Stroke Prevention by Aggressive Reduction in Cholesterol Levels Investigators . Statin treatment and stroke outcome in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. Stroke. 2009;40(11):3526-3531. doi:10.1161/STROKEAHA.109.557330 - DOI - PubMed
    1. Lau KK, Chua BJ, Ng A, et al. . Low-density lipoprotein cholesterol and risk of recurrent vascular events in Chinese patients with ischemic stroke with and without significant atherosclerosis. J Am Heart Assoc. 2021;10(16):e021855. doi:10.1161/JAHA.121.021855 - DOI - PMC - PubMed
    1. Amarenco P, Bogousslavsky J, Callahan A III, et al. ; Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators . High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549-559. doi:10.1056/NEJMoa061894 - DOI - PubMed

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