Rates and risk factors for major adverse cardiovascular and cerebrovascular events after stroke due to intracerebral hemorrhage: Systematic review and study-level meta-analysis

Background: Intracerebral hemorrhage (ICH) survivors are at increased risk of major adverse cardiovascular and cerebrovascular events (MACE) compared with population controls; however, little is known about the annual rates and risk factors for MACE. Methods: We searched Medline, Embase, and trial registries systematically in April 2024 for studies of adults with ICH, reporting either a MACE composite outcome or both ischemic and hemorrhagic outcomes, with at least one year of follow-up. We excluded studies limited to secondary ICH or isolated non-ICH intracranial hemorrhages. We used the QUIPS tool to assess studies’ risk of bias. The primary outcome was the rate of MACE. We used a random-effects meta-analysis to estimate the annual event rate (per 100 person-years, expressed as %) for each outcome. We conducted subgroup analyses and meta-regression to explore heterogeneity. Results: We included 26 studies, involving 198,289 ICH survivors. Individual studies’ reported annual rate of MACE ranged 4.2–14.6%. The pooled annual rate of recurrent ICH was 2.1% (95% confidence interval (CI) = 1.7–2.6; 26 studies; I 2 = 94%) and of ischemic stroke was 2.0% (95% CI = 1.5–2.7; 24 studies; I 2 = 95%). Meta-regression analyses identified one statistically significant association between a higher prevalence of atrial fibrillation and an increased risk of ischemic stroke. Discussion: The rates of recurrent ICH and ischemic stroke were comparable among ICH survivors, but evidence about other MACE outcomes remains limited. An individual participant data meta-analysis is needed to investigate the predictors of MACE outcomes, which may help inform risk stratification and prognosis among ICH survivors.