Abstract WP230: Calcium Channel Blockers Associated with Worse Functional Outcomes in Both Murine and Human Intracerebral Hemorrhage

Hypertension is common after ICH and while its management is critical, little data exist on specific pharmacologic agents and outcomes. We present the results of both an experimental mouse model and retrospective clinical study on the impact of class of antihypertensive medication on outcomes in ICH. We further investigated inflammation as a potential mechanism for differences among treatment groups in mice. Methods: Collagenase injection into the right striatum induced ICH in C57Bl/6 male mice. Mice were randomized to amlodipine (1.25 mg/mL), lisinopril (2.5 mg/mL), metoprolol (0.3125 mg/mL), DMSO (amlodipine vehicle), or water (other anti-hypertensives vehicle). Mice were dosed twice daily for 3 days beginning 1 hour after ICH. Blinded grid walk assessments were performed at day 3 for motor function. Immunofluorescence staining of perihematomal tissue for microglial activation (Iba1) and neutrophils (Ly6G) were quantified by blinded reviewers (total number of cells in 4 high-powered fields per mouse). Data from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) prospective clinical study were retrospectively analyzed for outcomes at 90 day follow-up, dichotomized into mRS <3 and >=3, using a multivariable logistic regression including age, ICH volume, premorbid mRS, race, past medical history, aspirin use, statin use, and antihypertensive medication class (yes/no for each). Only survivors at hospital discharge with outcome assessment at 90 days and medication use data at discharge and 90 days were included. Results: Mice treated with amlodipine had more left foot faults compared to DMSO (p<0.05) despite no differences in day 1 neurological deficit scores across treatment groups (Fig A). There were no differences in activated microglia or neutrophils. In the ERICH human dataset (n=1561), 808 patients remained on the same class of medication(s) from hospital discharge through 90 day follow up. We modeled this consistent exposure within each medication class to mimic the murine experiment. Age, premorbid mRS, history of prior ICH, Hispanic ethnicity, initial ICH volume, calcium channel blocker (CCB) use, and beta-blocker use were independently associated with poor outcome (Fig B). Conclusion: These results suggest that CCB use may be associated with worse functional recovery after murine and human ICH, while beta-blocker use was associated with worse recovery only in human ICH. Further work to validate and elucidate mechanisms is ongoing.