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Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data.

Salman, R and Frantzias, J and Lee, RJ and Lyden, PD and Battey, TWK and Ayres, AM and Goldstein, JN and Mayer, SA and Steiner, T and Wang, X and Arima, H and Hasegawa, H and Oishi, M and Godoy, DA and Masotti, L and Dowlatshahi, D and Rodriguez-Luna, D and Molina, CA and Jang, DK and Davalos, A and Castillo, J and Yao, X and Claassen, J and Volbers, B and Kazui, S and Okada, Y and Fujimoto, S and Toyoda, K and Li, Q and Khoury, J and Delgado, P and Sabín, JÁ and Hernández-Guillamon, M and Prats-Sánchez, L and Cai, C and Kate, MP and McCourt, R and Venkatasubramanian, C and Diringer, MN and Ikeda, Y and Worthmann, H and Ziai, WC and d'Esterre, CD and Aviv, RI and Raab, P and Murai, Y and Zazulia, AR and Butcher, KS and Seyedsaadat, SM and Grotta, JC and Martí-Fàbregas, J and Montaner, J and Broderick, J and Yamamoto, H and Staykov, D and Connolly, ES and Selim, M and Leira, R and Moon, BH and Demchuck, AM and Di Napoli, M and Fujii, Y and Anderson, CS and Rosand, J and Hanley, DF and Butcher, KS and Davis, S and Gregson, B and Lees, KR and Lyden, PD and Mayer, SA and Muir, KW and Steiner, T and Xie, P and Bakhshayesh, B and McDonald, M and Brott, T and Pennati, P and Parry-Jones, AR and Smith, CJ and Hopkins, SJ and Slevin, Mark and Campi, V and Singh, P and Papa, F and Popa-Wagner, A and Tudorica, V and Takagi, R and Teramoto, A and Weissenborn, K and Lanfermann, H (2018) Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data. The Lancet Neurology, 17 (10). pp. 885-894. ISSN 1474-4422


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Background 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. Methods 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. Findings 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). Interpretation 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.

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