Supplementary Material for: 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: Post-hoc analysis of INTERACT3 in patients with ICH surviving to Day 7. Associations of early ACE-I or angiotensin-II receptor blockers (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 6692 participants included in analyses, 2525 (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 to 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.