Prevalence, risk factors, and clinical outcomes of remote intracerebral hemorrhage after intravenous thrombolysis in acute ischemic stroke: a systematic review and meta-analysis

J Neurol. 2023 Feb;270(2):651-661. doi: 10.1007/s00415-022-11414-2. Epub 2022 Oct 5.

Abstract

Background: Hemorrhagic transformation (HT) is a common complication of alteplase treatment. However, the prevalence rate, risk factors, and clinical outcomes of remote intracerebral hemorrhage (rICH) after intravenous thrombolysis in acute ischemic stroke are not well understood.

Methods: Following a previously registered protocol, the PubMed, Web of Science, and Embase databases were systematically searched to identify relevant literature up to June 2022. Cohort studies reporting thrombolysis-related rICH in patients with acute ischemic stroke were included. Random effects models were used to calculate pooled prevalence rate, mean difference (MD) or odds ratio (OR) with corresponding 95% confidence interval (CI).

Results: Fourteen studies with 52,610 patients were included in this meta-analysis. The pooled rICH prevalence was 3.2% (95% CI 3.1-3.4%). Compared to patients without intracerebral hemorrhage (ICH), those with rICH were older, more likely to be female, and had a higher proportion of prior stroke, chronic heart failure and cardioembolism, and higher diastolic blood pressure. Small vessel disease markers (e.g., white matter hyperintensities and cerebral microbleeds) were strongly associated with rICH. The presence of rICH decreased the likelihood of favorable outcomes (OR 0.36, 95% CI 0.31-0.41) and increased the risk of mortality (OR 4.37, 95% CI 2.86-6.67).

Conclusions: Although rICH is uncommon after intravenous thrombolysis, its presence can lead to worse functional outcomes and higher mortality in acute ischemic stroke. Patients at high risk of rICH must be identified based on potential risk factors.

Keywords: Acute ischemic stroke; Alteplase; Hemorrhage transformation; Intravenous thrombolysis; Remote intracerebral hemorrhage.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Brain Ischemia* / complications
  • Brain Ischemia* / drug therapy
  • Brain Ischemia* / epidemiology
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / epidemiology
  • Female
  • Fibrinolytic Agents / adverse effects
  • Humans
  • Ischemic Stroke* / complications
  • Ischemic Stroke* / drug therapy
  • Ischemic Stroke* / epidemiology
  • Male
  • Prevalence
  • Risk Factors
  • Thrombolytic Therapy / adverse effects
  • Thrombolytic Therapy / methods
  • Tissue Plasminogen Activator / adverse effects
  • Treatment Outcome

Substances

  • Fibrinolytic Agents
  • Tissue Plasminogen Activator