Association Between Hematoma Volume and Risk of Subsequent Ischemic Stroke: A MISTIE III and ATACH-2 Analysis.

Background: Nontraumatic intracerebral hemorrhage (ICH) is independently associated with a long-term increased risk of major arterial ischemic events. While the relationship between ICH location and ischemic risk has been studied, 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-2) trials. The exposure was hematoma volume, treated as a continuous measure in the primary analysis, and dichotomized by the median in the secondary analyses. The outcome was a symptomatic, clinically overt 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 1470 patients with ICH, the mean age was 61.7 (SD, 12.8) years, and 574 (38.3%) were female. The median hematoma volume was 17.3 mL (interquartile range, 7.2-35.7). During a median follow-up of 107 days (interquartile range, 91-140), a total of 30 ischemic strokes occurred, of which 22 were in patients with a median ICH volume of ≥17.3 mL and a cumulative incidence of 4.6% (95% CI, 3.1-7.1). Among patients with a median ICH volume <17.3 mL, there were 8 ischemic strokes with a cumulative incidence of 3.1% (95% CI, 1.7-6.0). In primary analyses using adjusted Cox regression models, ICH volume was associated with an increased risk of ischemic stroke (hazard ratio, 1.02 per mL increase [95% CI, 1.01-1.04]). In secondary analyses, ICH volume of ≥17.3 mL was associated with an increased risk of ischemic stroke (hazard ratio, 2.5 [95% CI, 1.1-7.2]), compared with those with an ICH volume <17.3 mL.
Conclusions: In a heterogeneous cohort of patients with ICH, initial hematoma volume was associated with a heightened short-term risk of ischemic stroke.
Competing Interests: Disclosures Dr Harris reports stock holdings in Eli LIlly and stock holdings in GlaxoSmithKline. Dr Iadecola has served on the scientific advisory board for Broadview Ventures. Dr Falcone has received grants from the National Institutes of Health (NIH) and the American Heart Association outside of the submitted work. Dr Sheth reports compensation from Cerevasc for consultant services; service as President for Advanced Innovation in Medicine; a patent pending for Stroke wearables licensed to Alva Health. Dr Goldstein reports compensation from Cayuga for consultant services; compensation from Prothya for consultant services; compensation from AstraZeneca for consultant services; and compensation from Lumosa for consultant services. Dr Qureshi reports compensation from Chiesi Farmaceutici for consultant services and compensation from Chiesi USA, Inc, for consultant services. Dr Awad reports compensation from Medicoegal consulting for expert witness services. Dr Hanley reports grants from US Department of Defense; grants from National Institute of Neurological Disorders and Stroke (NINDS); grants from NINDS to other; grants from NINDS; compensation from Neurelis, Inc, for consultant services; grants from National Center for Advancing Translational Sciences; grants from NINDS; gifts from Jeffrey and Harriet Legum Professorship in Acute Neurological Medicine at Johns Hopkins University. Dr Kamel is a co-principal investigator for the ARCADIA trial ([Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke]; NIH/NINDS U01NS095869), which received in-kind study drug from the Bristol Myers Squibb-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics; other funding from NIH (R01HL144541, R01NS123576, and U01NS106513); Deputy Editor for JAMA Neurology; clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; end point adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group. Dr Ziai has received grants from the NIH, serves as the Associate Editor of Neurocritical Care. Dr Murthy has received grant support from the NIH. The other authors report no conflicts.