Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data.
Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data.
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DOI：
10.1016/s1474-4422(18)30253-9
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发表时间：
2018-10
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通讯作者：
ICH Growth Individual Patient Data Meta-analysis Collaborators
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Al-Shahi Salman R;Frantzias J;Lee RJ;Lyden PD;Battey TWK;Ayres AM;Goldstein JN;Mayer SA;Steiner T;Wang X;Arima H;Hasegawa H;Oishi M;Godoy DA;Masotti L;Dowlatshahi D;Rodriguez-Luna D;Molina CA;Jang DK;Davalos A;Castillo J;Yao X;Claassen J;Volbers B;Kazui S;Okada Y;Fujimoto S;Toyoda K;Li Q;Khoury J;Delgado P;Sabín JÁ;Hernández-Guillamon M;Prats-Sánchez L;Cai C;Kate MP;McCourt R;Venkatasubramanian C;Diringer MN;Ikeda Y;Worthmann H;Ziai WC;d'Esterre CD;Aviv RI;Raab P;Murai Y;Zazulia AR;Butcher KS;Seyedsaadat SM;Grotta JC;Martí-Fàbregas J;Montaner J;Broderick J;Yamamoto H;Staykov D;Connolly ES;Selim M;Leira R;Moon BH;Demchuk AM;Di Napoli M;Fujii Y;Anderson CS;Rosand J;VISTA-ICH Collaboration;ICH Growth Individual Patient Data Meta-analysis Collaborators
脑内出血的增长与不良的临床结果相关，并且是改善结果的治疗目标。我们的目的是确定脑内出血增长的绝对风险和预测因素，开发和验证预测模型，并评估 CT 血管造影的附加值。在对 OVID MEDLINE 的系统回顾中，并额外手工检索了 1970 年 1 月 1 日至 2015 年 12 月 31 日的相关研究参考书目，我们确定了观察队列和采用重复扫描方案的随机试验，其中包括至少 10 名急性脑出血患者。我们从相应作者那里寻求了18岁或以上患者的个体患者水平数据，这些数据来自最初在0·5-24小时内进行的脑成像，并在症状出现后不到6天内重复，这些患者的基线脑内出血量小于150 mL，并且没有接受可能减少脑内出血量的急性治疗。我们在四个亚组患者的开发和验证队列中使用多变量逻辑回归模型估计了脑内出血增长（定义为重复成像时脑内出血量增加> 6 mL）主要结局的绝对风险和预测因素，采用分层方法：脑内出血发作时未接受抗凝治疗的患者（构成最大的亚组），脑内出血时接受抗凝治疗的患者。脑出血发作时的患者队列中至少包括一些在脑出血发作时接受抗凝治疗的患者，以及已知脑内出血发作时抗凝治疗信息和急性 CT 血管造影斑点标志的患者。在确定的 4191 项研究中，有 77 项符合纳入条件。总体而言，36 个队列 (47%) 提供了 5435 名符合条件的患者的数据。其中 5076 名患者在症状出现时未接受抗凝治疗（中位年龄 67 岁，IQR 56-76），其中 1009 名 (20%) 出现脑内出血。具有抗血小板治疗使用数据、抗凝治疗使用数据以及症状出现时 CT 血管造影斑征评估的患者多变量模型显示，从症状出现到基线成像的时间（优势比 0·50，95% CI 0·36–0·70；p<0·0001）、基线成像的脑出血量（7·18、4·46–11·60； p<0·0001）、抗血小板药物的使用（1·68、1·06–2·66；p=0·026）和抗凝剂的使用（3·48、1·96–6·16；p<0·0001）是脑内出血增长的独立预测因素（C 指数 0·78，95% CI 0·75–0·82）。在模型中添加 CT 血管造影点征（比值比 4·46，95% CI 2·95–6·75；p<0·0001）使 C 指数增加 0·05（95% CI 0·03–0·07）。在这项大型患者层面的荟萃分析中，使用四个或五个预测因子的模型具有良好的辨别能力。这些模型可以告知临床实践中对患者进行观察的位置和频率，解释先前随机试验中的治疗效果，并指导未来试验的设计。英国医学研究委员会和英国心脏基金会。
Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography. In a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known. Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07). In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials. UK Medical Research Council and British Heart Foundation.