Association of Angiotensin Inhibitors with Improved Outcome after Acute Intracerebral Hemorrhage: Secondary Analysis of the INTERACT3 Trial.

INTRODUCTION: Drug screening with a zebrafish model of acute intracerebral hemorrhage (ICH) identified a neuroprotective effect of angiotensin converting enzyme inhibitor (ACE-I) drugs. We identified an association of early ACE-I treatment and favorable 90-day functional outcome in participants of the second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial. We aimed to confirm a relation between angiotensin inhibitors and good outcome in the larger, third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) dataset. METHODS: This is a post hoc analysis of INTERACT3 in patients with ICH surviving to day 7. Associations of early ACE-I or angiotensin-II receptor blocker (ARB) treatment and neurological impairment (National Institutes of Health Stroke Scale [NIHSS] scores) at day 7 and functional recovery (modified Rankin Scale [mRS] scores) at 6 months were tested in multiple regression and ordinal regression models, respectively, with adjustment for confounding variables. RESULTS: Of 6,692 participants included in analyses, 2,525 (36.2%) received ACE-I/ARB treatment by day 7. Treatment with an ACE-I/ARB (vs. no ACE-I/ARB) was significantly and independently associated with lower NIHSS scores at day 7 (β-coefficient -1.17, 95% confidence interval [CI] -1.59 to -0.74; p < 0.001) and better mRS scores at 6 months (odds ratio 0.83, 95% CI 0.75-0.93; p = 0.0007). CONCLUSION: Early treatment with an angiotensin inhibitor is associated with improved outcome after ICH. Further research is needed to test for heterogeneity by ACE-I/ARB drug and treatment window to plan a clinical trial in ICH.