Cerebral Microbleeds and the Effect of Early Antihypertensive Treatment in Patients with Acute Ischemic Stroke: A Secondary Analysis of the CATIS-2 Trial

Abstract Background and Objectives To explore whether the presence, burden or distribution of cerebral microbleeds (CMBs) modifies the effect of early versus delayed antihypertensive treatment on clinical outcomes in acute ischemic stroke (AIS) patients. Methods A secondary analysis of the China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) trial was performed. Participants with baseline cerebral magnetic resonance imaging (MRI) data for CMB evaluation were included. The primary outcome was functional dependency or death at 90 days, defined as a modified Rankin Scale (mRS) score ≥3. Results Among 815 eligible participants (mean age 62.4 years; 34.5% female), 396 (48.6%) had at least one CMB. The presence of strictly deep CMBs was associated with an increased risk of functional dependency or death at 90 days compared to the absence of CMBs (15.3% vs 7.9%; adjusted odds ratio aOR 1.92, 95% CI 1.08-3.40, P =0.03). Early versus delayed antihypertensive treatment significantly increased the risk of functional dependency or death in patients with CMBs (17.1% vs 8.7%; aOR 2.17, 95% CI 1.16-4.07; P =0.02). This effect was particularly pronounced among patients with moderate-to-severe CMBs (17.5% vs 6.6%; aOR, 2.85; 95% CI, 1.06–7.67; P =0.04) and strictly deep CMBs (20.8% vs 9.0%; aOR, 2.76; 95% CI, 1.15–6.64; P =0.02). However, no statistically significant interaction was observed between CMBs and treatment assignment for the primary outcome ( p interaction >0.05). Conclusions This secondary analysis of CATIS-2 indicates that the presence of CMBs, particularly those predominantly located in deep regions or with a greater burden, may increase the risk of adverse clinical outcomes following early antihypertensive treatment in AIS patients. These findings highlight the imperative for further research on individualized blood pressure (BP) management strategies in AIS patients with CMBs. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03479554 .