Abstract

Background: Non-traumatic intracerebral hemorrhage (ICH) is independently associated with long-term increased risk of major arterial ischemic events. Whether hematoma volume influences this risk is poorly understood. Methods: We pooled individual patient data from the MISTIE III (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3) and the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage) trials. The exposure was hematoma volume. In the primary analysis, hematoma volume was treated as a continuous measure after natural logarithmic transformation to approximate linearity, and in the secondary analysis, it was dichotomized by the median. The outcome was an ischemic stroke, adjudicated centrally within each trial. We evaluated the association between hematoma volume and the risk of an ischemic stroke using Cox regression analyses after adjustment for demographics, vascular comorbidities, and ICH characteristics. Results: Of 1,499 ICH patients, the mean age was 61.7 (SD, 12.8) years and 574 (38.3%) were female. The median hematoma volume was 17.3 mL (IQR, 7.2-35.7). During a median follow up of 107 days (IQR, 91-140), 30 ischemic strokes occurred of which 22 were in patients with median ICH volume > 17.3 mL with a cumulative incidence of 4.6% (95% CI, 3.1-7.1). Among patients with median ICH volume < 17.3 mL, there were 8 ischemic strokes with a cumulative incidence of 3.1% (95% CI, 1.7-6.0). Using adjusted Cox regression models, log-transformed ICH volume (continuous measure) was associated with an increased risk of ischemic stroke (HR, 1.5 per log-unit increase; 95% CI, 1.1-2.8). Similarly, ICH volume > 17.3 mL was associated with an increased risk of ischemic stroke (HR, 2.5; 95% CI, 1.1-7.2), compared to those with an ICH volume < 17.3 mL. Conclusions: In a heterogeneous cohort of ICH patients, initial hematoma volume was associated with a heightened risk of subsequent ischemic stroke.

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