Supplementary Material for: Lipid-Lowering Pretreatment and Outcome Following Intravenous Thrombolysis for Acute Ischaemic Stroke: A Post Hoc Analysis of the Enhanced Control of Hypertension and Thrombolysis Stroke Study Trial

<b><i>Background:</i></b> Debate exists as to whether statin pretreatment confers an increased risk of 90-day mortality and symptomatic intracranial haemorrhage (sICH) in acute ischaemic stroke (AIS) patients treated with intravenous thrombolysis. We assessed the effects of undifferentiated lipid-lowering pretreatment on outcomes and interaction with low-dose versus standard-dose alteplase in a post hoc subgroup ­analysis of the Enhanced Control of Hypertension and Thrombolysis Stroke Study. <b><i>Methods:</i></b> In all, 3,284 thrombolysis-eligible AIS patients (mean age 66.6 years; 38% women), with information on lipid-lowering pretreatment, were randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 h of symptom onset. Of the total number of patients, 615 (19%) received statin or other lipid-lowering pretreatment. The primary clinical outcome was combined endpoint of death or disability (modified Rankin Scale scores 2–6) at 90 days. <b><i>Results:</i></b> Compared with patients with no lipid-lowering pretreatment, those with lipid-lowering pretreatment were significantly older, more likely to be non-Asian and more likely to have a medical history including vascular co-morbidity. After propensity analysis assessment and adjustment for important baseline variables at the time of randomisation, as well as imbalances in management during the first 7 days of hospital admission, there were no significant differences in mortality (OR 0.85; 95% CI 0.58–1.25, <i>p</i> = 0.42), or in overall ­90-day death and disability (OR 0.85, 95% CI 0.67–1.09, <i>p</i> = 0.19), despite a significant decrease in sICH among those with ­lipid-lowering pretreatment according to the European Co-operative Acute Stroke Study 2 definition (OR 0.49, 95% CI 0.28–0.83, <i>p</i> = 0.009). No differences in key efficacy or safety outcomes were seen in patients with and without lipid-lowering pretreatment between low- and standard-dose alteplase arms. <b><i>Conclusions:</i></b> Lipid-lowering pretreatment is not associated with adverse outcome in AIS patients treated with intravenous alteplase, whether assessed by 90-day death and disability or death alone.

<b><i>背景：</i></b> 目前关于他汀类药物预处理是否会增加急性缺血性脑卒中（acute ischaemic stroke, AIS）患者接受静脉溶栓（intravenous thrombolysis）治疗后的90天死亡率与症状性颅内出血（symptomatic intracranial haemorrhage, sICH）风险，学界尚存争议。本研究依托《高血压强化控制与脑卒中溶栓研究》的事后亚组分析，评估了非选择性调脂预处理对预后的影响，以及其与低剂量与标准剂量阿替普酶（alteplase）的交互作用。<b><i>方法：</i></b> 本研究共纳入3284名符合溶栓指征的急性缺血性脑卒中患者（平均年龄66.6岁；女性占比38%），所有患者均在症状发作后4.5小时内被随机分配接受低剂量（0.6 mg/kg）或标准剂量（0.9 mg/kg）静脉阿替普酶治疗，且均具备调脂预处理相关信息。其中615名患者（占总人群的19%）接受了他汀类或其他调脂药物预处理。本研究的主要临床结局为90天时死亡或残疾的复合终点（改良Rankin量表评分2~6分）。<b><i>结果：</i></b> 与未接受调脂预处理的患者相比，接受调脂预处理的患者年龄显著更高，非亚裔占比更高，且更常合并血管共病等既往病史。经倾向评分分析校正随机分组时的重要基线变量，以及入院后前7天的治疗失衡情况后，尽管根据欧洲急性脑卒中协作研究2（European Co-operative Acute Stroke Study 2）定义，接受调脂预处理的患者的症状性颅内出血发生率显著降低（比值比（odds ratio, OR）=0.49，95%置信区间（confidence interval, CI）：0.28~0.83，<i>p</i>=0.009），但两组患者的死亡率（OR=0.85，95%CI：0.58~1.25，<i>p</i>=0.42）、整体90天死亡与残疾复合结局（OR=0.85，95%CI：0.67~1.09，<i>p</i>=0.19）均无显著差异。在低剂量与标准剂量阿替普酶组中，接受与未接受调脂预处理的患者在关键疗效或安全性结局上均无显著差异。<b><i>结论：</i></b> 无论以90天死亡与残疾复合终点，还是单纯死亡作为评估指标，接受静脉阿替普酶治疗的急性缺血性脑卒中患者中，调脂预处理均与不良预后无关联。