Cerebral Amyloid Angiopathy and the Risk of Hematoma Expansion

Abstract

Objective: We assessed whether hematoma expansion (HE) and favorable outcome differ according to type of intracerebral hemorrhage (ICH).

Methods: Among participants with ICH enrolled in the TICH-2 (Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage) trial, we assessed baseline scans for hematoma location and presence of cerebral amyloid angiopathy (CAA) using computed tomography (CT, simplified Edinburgh criteria) and magnetic resonance imaging (MRI; Boston criteria) and categorized ICH as lobar CAA, lobar non-CAA, and nonlobar. The main outcomes were HE and favorable functional outcome. We constructed multivariate regression models and assessed treatment effects using interaction terms.

Results: A total of 2,298 out of 2,325 participants were included with available CT (98.8%; median age = 71 years, interquartile range = 60-80 years; 1,014 female). Additional MRI was available in 219 patients (9.5%). Overall, 1,637 participants (71.2%) had nonlobar ICH; the remaining 661 participants (28.8%) had lobar ICH, of whom 202 patients had lobar CAA-ICH (8.8%, 173 participants according to Edinburgh and 29 participants according to Boston criteria) and 459 did not (lobar non-CAA, 20.0%). For HE, we found a significant interaction of lobar CAA ICH with time from onset to randomization (increasing risk with time, p_interaction < 0.001) and baseline ICH volume (constant risk regardless of volume, p_interaction < 0.001) but no association between type of ICH and risk of HE or favorable outcome. Tranexamic acid significantly reduced the risk of HE (adjusted odds ratio = 0.7, 95% confidence interval = 0.6-1.0, p = 0.020) without statistically significant interaction with type of ICH (p_interaction = 0.058). Tranexamic acid was not associated with favorable outcome.

Interpretation: Risk of HE in patients with lobar CAA-ICH was not independently increased but seems to have different dynamics compared to other types of ICH. The time window for treatment of CAA-ICH to prevent HE may be longer. ANN NEUROL 2022;92:921-930.

FIGURE 1

Risk of hematoma expansion (HE) according to type of intracerebral hemorrhage (ICH). Percentage of participants with HE (≥33% or ≥6ml; upper left panel) and absolute hematoma volume at baseline and 24‐hour follow‐up computed tomography (upper right panel). There was a significant interaction on the risk of HE of type of ICH with hematoma volume (lower left panel, in contrast to other types of ICH, the risk of HE seems constant for lobar cerebral amyloid angiopathy [CAA]‐ICH regardless of baseline volume, p _interaction < 0.001) and time to randomization (lower right panel, increasing risk with time in participants with lobar CAA‐ICH, p _interaction <0.001). Predicted probability was assessed using multivariate analysis adjusting for covariates (age, sex, National Institutes of Health Stroke Scale at baseline, systolic blood pressure at baseline, intraventricular hemorrhage [IVH] at baseline, prior antiplatelet therapy, time from onset to randomization, baseline blood glucose, prior statin therapy, and baseline ICH volume) and interaction terms for time and volume with type of ICH. CI = confidence interval. [Color figure can be viewed at www.annalsofneurology.org]

FIGURE 2

Risk of hematoma expansion (left) and chance of good functional outcome (modified Rankin Scale = 0–2 at 3 months; right) according to type of intracerebral hemorrhage (ICH) in participants receiving placebo or tranexamic acid (TXA). We did not observe any statistically significant interaction between treatment with tranexamic acid and type of ICH, either on risk of hematoma expansion (p _interaction = 0.214) or on good functional outcome (p _interaction = 0.710). CAA = cerebral amyloid angiopathy.

FIGURE 3

Distribution of modified Rankin Scale (mRS) scores at 3 months per type of intracerebral hemorrhage (ICH). CAA = cerebral amyloid angiopathy. [Color figure can be viewed at www.annalsofneurology.org]

FIGURE 4

There was no statistically significant interaction between type of intracerebral hemorrhage (ICH) and hematoma volume (left panel; p _interaction = 0.214) or time to randomization (right panel; p _interaction = 0.359) on chance of favorable outcome (modified Rankin Scale [mRS] = 0–2 at 3 months). Predicted probability was assessed using multivariate analysis adjusting for covariates (age, sex, National Institutes of Health Stroke Scale at baseline, systolic blood pressure at baseline, intraventricular hemorrhage at baseline, prior antiplatelet therapy, time from onset to randomization, prior statin therapy, baseline blood glucose, and baseline ICH volume) and interaction terms for time and volume with type of ICH. CAA = cerebral amyloid angiopathy; CI = confidence interval. [Color figure can be viewed at www.annalsofneurology.org]