Quantity of Cerebral Microbleeds, Antiplatelet Therapy, and Intracerebral Hemorrhage Outcomes: A Systematic Review and Meta-analysis

Background and purpose: Cerebral microbleeds (CMBs) increase future intracerebral hemorrhage (ICH) risk after ischemic stroke (IS) or transient ischemic attack (TIA). However, whether CMB-related ICH risk depends on CMB quantity, CMB location, or antithrombotic agents is unclear. We performed a systematic review and meta-analysis to investigate CMB-related ICH risk, stratifying patients according to the quantity of CMB, the location of CMB, and the type of antithrombotic therapy used. Methods: Literature databases were searched for prospective cohorts reporting ICH outcomes in patients with IS or TIA with baseline CMB evaluation. We calculated pooled relative ratios (RRs) for ICH among patients with and without CMBs. Pooled RRs of CMB-related ICH were further calculated in subgroups stratified by CMB quantity, CMB location, and antithrombotic therapy. Results: Among the 10 included studies, the pooled RR of future ICH was 7.73 (95% confidence interval [CI], 4.07-14.70; P<.001) in CMB versus non-CMB patients. Subgroup analysis revealed that compared with non-CMB patients, multiple-CMB patients were at an increased risk for future ICH (RR = 8.02; 95% CI, 3.21-20.01; P<.001), whereas single-CMB patients did not incur this risk (RR = 2.33; 95% CI, .63-8.63; P=.205). A strong association was found between CMB presence and subsequent ICH in antiplatelet users (RR = 16.56; 95% CI, 3.68-74.42; P<.001). Studies on CMB-related ICH according to CMB locations and in anticoagulant users are lacking for subgroup analysis. Conclusion: Our study revealed that patients with IS or TIA with multiple CMBs may incur a higher risk of future ICH, and the presence of CMBs in patients with IS or TIA using antiplatelet agents may significantly increase the subsequent ICH risk.