Functional outcomes after reperfusion therapy for acute ischemic stroke: Is there a modifying effect of renin-angiotensin-aldosterone system inhibition?

To determine whether in-hospital renin–angiotensin–aldosterone system inhibitor (RAASi) use modifies the association between reperfusion strategy and 90-day functional outcomes in acute ischemic stroke (AIS), in both the overall cohort and a large vessel occlusion (LVO) subgroup. We retrospectively studied adults admitted with AIS between August 1, 2022, and July 31, 2024, who received intravenous thrombolysis (IVT) or mechanical thrombectomy (MT). RAASi exposure was defined as any in-hospital administration of an ACE inhibitor or angiotensin receptor blocker. The primary outcome was 90-day modified Rankin Scale (mRS). Because the proportional odds assumption was violated, partial proportional odds regression was used. Adjusted models included age, sex, admission systolic blood pressure, NIHSS score, hypertension, diabetes mellitus, and heart failure. The primary analysis tested interaction terms between RAASi exposure and reperfusion strategy in the full cohort and separately in the LVO subgroup. Among 305 patients (139 RAASi; 166 non-RAASi), 247 (81.0%) had LVO. Age, sex, and baseline NIHSS were similar between groups, although RAASi patients had higher rates of heart failure and greater antihypertensive use. RAASi exposure alone was not independently associated with 90-day functional outcome. In adjusted models, IVT was associated with improved outcome (OR 0.50; 95% CI 0.27–0.93), whereas MT was associated with higher odds of worse outcome in this observational cohort (OR 1.98; 95% CI 1.07–3.65). In the full cohort, interaction analyses suggested attenuation of thrombolytic benefit among patients receiving RAASi (RAASi × IVT OR 1.38; 95% CI 0.61–3.12) and a differential pattern in the MT group (RAASi × MT OR 0.72; 95% CI 0.32–1.64); however, neither interaction was statistically significant. A parallel interaction analysis restricted to the LVO subgroup demonstrated similar attenuation patterns without statistical significance. In this predominantly LVO AIS cohort, RAASi use was not independently associated with improved 90-day outcomes. Although interaction testing did not demonstrate statistical significance, directionally similar attenuation patterns were observed across the overall and LVO analyses. These findings are hypothesis-generating and require validation in larger, prospectively characterized cohorts.