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

  1. Zilin Zhao
  2. Xuewei Xie
  3. Yuesong Pan
  4. Mengxing Wang
  5. Yufei Wei
  6. Ximing Nie
  7. Aili Wang
  8. Dacheng Liu
  9. Wanying Duan
  10. Xin Liu
  11. Zhe Zhang
  12. Jingyi Liu
  13. Lina Zheng
  14. Minghua Wang
  15. Yong Jiang
  16. Jing Jing
  17. Xia Meng
  18. Katherine Obst
  19. Chung-Shiuan Chen
  20. Hao Li
  21. David Wang
  22. Yilong Wang
  23. Yonghong Zhang
  24. Jiang He
  25. Yongjun Wang
  26. Liping Liu
  27. the CATIS-2 Investigators
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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 .

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  1. Version published to 10.1101/2025.08.13.25333633 on medRxiv