Outcomes in Antiplatelet-Associated Intracerebral Hemorrhage in the TICH-2 Randomized Controlled Trial

Abstract

Background Antiplatelet therapy increases the risk of hematoma expansion in intracerebral hemorrhage (ICH) while the effect on functional outcome is uncertain. Methods and Results This is an exploratory analysis of the TICH-2 (Tranexamic Acid in Intracerebral Hemorrhage-2) double-blind, randomized, placebo-controlled trial, which studied the efficacy of tranexamic acid in patients with spontaneous ICH within 8 hours of onset. Multivariable logistic regression and ordinal regression were performed to explore the relationship between pre-ICH antiplatelet therapy, and 24-hour hematoma expansion and day 90 modified Rankin Scale score, as well as the effect of tranexamic acid. Of 2325 patients, 611 (26.3%) had pre-ICH antiplatelet therapy. They were older (mean age, 75.7 versus 66.5 years), more likely to have ischemic heart disease (25.4% versus 2.7%), ischemic stroke (36.2% versus 6.3%), intraventricular hemorrhage (40.2% versus 27.5%), and larger baseline hematoma volume (mean, 28.1 versus 22.6 mL) than the no-antiplatelet group. Pre-ICH antiplatelet therapy was associated with a significantly increased risk of hematoma expansion (adjusted odds ratio [OR], 1.28; 95% CI, 1.01-1.63), a shift toward unfavorable outcome in modified Rankin Scale (adjusted common OR, 1.58; 95% CI, 1.32-1.91) and a higher risk of death at day 90 (adjusted OR, 1.63; 95% CI, 1.25-2.11). Tranexamic acid reduced the risk of hematoma expansion in the overall patients with ICH (adjusted OR, 0.76; 95% CI, 0.62-0.93) and antiplatelet subgroup (adjusted OR, 0.61; 95% CI, 0.41-0.91) with no significant interaction between pre-ICH antiplatelet therapy and tranexamic acid (P interaction=0.248). Conclusions Antiplatelet therapy is independently associated with hematoma expansion and unfavorable functional outcome. Tranexamic acid reduced hematoma expansion regardless of prior antiplatelet therapy use. Registration URL: https://www.isrctn.com; Unique identifier: ISRCTN93732214.

Keywords: antiplatelet; cerebral hemorrhage; hematoma expansion; randomized controlled trial; tranexamic acid.

Figure 1. Functional outcome at day 90 after intracerebral hemorrhage in antiplatelet vs no antiplatelet subgroups (adjusted common odds ratio, 1.58; 95% CI 1.32–1.91; P<0.001).

Analysis was ordinal logistic regression, adjusted for age, sex, systolic blood pressure, National Institutes of Health Stroke Scale, onset to randomization time, intraventricular hemorrhage, treatment group, and country.

Figure 2. Effect of tranexamic acid on hematoma expansion, death and death or dependence (modified Rankin Scale score [mRS] >3) at day 90 stratified by prior use of antiplatelet therapy.

Analysis was multivariable binary logistic regression with adjustment for age, sex, systolic blood pressure, National Institutes of Health Stroke Scale, onset to randomization time, intraventricular hemorrhage, and country for outcome of death and mRS >3 at day 90 with additional variable of baseline hematoma volume for hematoma expansion. Figure differed from previously published ¹⁴ as current analysis included additional clinical scans; and the presence of intraventricular hemorrhage was based on expert radiologists' adjudication rather than investigator reported. aOR indicates adjusted odds ratio; and mRS, modified Rankin Scale.