Antihypertensive Medication Class and Functional Outcomes After Nonlobar Intracerebral Hemorrhage
Authors: Ridha Mohamed , Burke James F. , Sekar Padmini , Woo Daniel , Hannawi Yousef 
Published: February 2025

Importance

Hypertension is the predominant pathology underlying nonlobar intracerebral hemorrhage (ICH), and antihypertensive agents have distinct biological implications for cerebral microvasculature. It is unknown if the class of antihypertensive medications initiated after ICH affects functional outcome beyond blood pressure (BP) control.

Objective

To ascertain the association between the class of antihypertensive agents initiated during hospitalization and 90-day functional outcome in nonlobar ICH.

Design, Setting, and Participants

This cohort study uses data from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a case-control cohort study investigating ICH risk factors among Hispanic, non-Hispanic Black (hereafter Black), and non-Hispanic White (hereafter White) populations at 42 US hospitals from 2010 to 2015. Data for this analysis were examined from May to September 2024. ERICH study participants were selected for the present analysis if they survived hospitalization and had available covariate and outcome data. Individuals with complications that would limit antihypertensive choice were excluded.

Exposures

Initiation of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), calcium channel blocker, β-blocker, thiazide diuretic, and other antihypertensive medications during index hospitalization.

Main Outcomes and Measures

Primary outcome was a favorable functional outcome, defined as a 90-day (follow-up) modified Rankin Score score of 0 to 2 (score range: 0 [indicating no disability] to 6 [indicating death]). Mixed-effects logistic regression adjusted for demographic characteristics, medical history, ICH characteristics, BP measurement, total number of antihypertensive medications, and hospitalization site was used to calculate the odds of favorable functional outcome.

Results

Of the 1561 ERICH study participants in the analytic cohort, 1079 had nonlobar and 482 had lobar ICH. Among the 1079 participants in the nonlobar ICH group (mean [SD] age, 58.5 [12.9] years; 676 males [62.6%]; 429 Hispanic [39.8%], 388 Black [36.0%], and 262 White [24.4%] individuals), a total of 407 (37.7%) ACEIs or ARBs, 419 (38.8%) β-blockers, 503 (46.6%) calcium channel blockers, 180 (16.7%) thiazide diuretics, and 277 (25.7%) other antihypertensive classes were initiated during hospitalization (median [IQR], 3 [2-3] agents at discharge). At follow-up, 481 participants (44.6%) had a favorable functional outcome. Initiation of ACEI or ARB was associated with higher odds of favorable functional outcome (adjusted OR [AOR], 1.49; 95% CI, 1.08-2.05; P = .01). No other antihypertensive class was associated with functional outcome. Findings were consistent across several sensitivity analyses. The interaction with ACEI or ARB was mediated by the presence of radiographic features of cerebral small vessel disease (AOR, 3.04; 95% CI, 1.01-9.19; P = .049). No association with class of antihypertensive agent was observed in lobar ICH.

Conclusions and Relevance

This large cohort study found that initiation of ACEI or ARB was associated with favorable 90-day functional outcomes after nonlobar ICH. This finding supports a medication class–specific benefit in hypertensive arteriopathy.