Meta-analysis of intracranial hemorrhage in acute coronary syndromes: incidence, predictors, and clinical outcomes

J Am Heart Assoc. 2015 Jun 18;4(6):e001512. doi: 10.1161/JAHA.114.001512.


Background: Little is known about the incidence, predictors, or outcomes of intracranial hemorrhage (ICH) in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). We aimed to determine the incidence and timing of ICH, characterize the location of ICH, and identify independent baseline predictors of ICH in NSTE ACS patients.

Methods and results: We pooled patient-level data from 4 contemporary antithrombotic therapy trials. Multivariable modeling identified independent predictors of ICH. ICHs were adjudicated by a clinical events committee. Of 37 815 patients, 135 (0.4%) had an ICH. The median (25th, 75th percentiles) follow-up was 332 (184, 434) days but differed across trials. Locations of ICH were intracerebral (50%), subdural (31%), subarachnoid (18.5%), and intraventricular (11%). Independent predictors of ICH were older age (HR per 10 years, 1.61; 95% CI, 1.35 to 1.91); prior stroke/transient ischemic attack; HR, 1.95; 95% CI, 1.14 to 3.35), higher systolic blood pressure; HR per 10 mm Hg increase, 1.09; 95% CI, 1.01 to 1.18), and larger number of antithrombotic agents (HR per each additional agent, 2.06; 95% CI, 1.49 to 2.84). Of all ICHs, 45 (33%) were fatal.

Conclusions: In patients with NSTE ACS enrolled in recent clinical trials of antithrombotic therapies, ICH was uncommon. Patients with older age, prior transient ischemic attack/stroke, higher systolic blood pressure, or larger number of antithrombotic agents were at increased risk. One-third of patients with ICH died. These data may be useful to trialists and data and safety monitoring committees for trial conduct and monitoring.

Clinical trial registration: URL: Unique identifiers: TRACER: NCT00527943, PLATO: NCT00391872, APPRAISE-2: NCT00831441, TRILOGY ACS: NCT00699998.

Keywords: acute coronary syndromes; clinical outcomes; intracranial hemorrhage; systematic review.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Acute Coronary Syndrome / complications*
  • Age Factors
  • Aged
  • Cerebral Hemorrhage / epidemiology
  • Cerebral Hemorrhage / etiology
  • Cerebral Hemorrhage / mortality
  • Female
  • Fibrinolytic Agents / adverse effects
  • Humans
  • Hypertension / complications
  • Incidence
  • Intracranial Hemorrhages / epidemiology
  • Intracranial Hemorrhages / etiology*
  • Intracranial Hemorrhages / mortality
  • Male
  • Middle Aged
  • Risk Factors
  • Subarachnoid Hemorrhage / epidemiology
  • Subarachnoid Hemorrhage / etiology
  • Subarachnoid Hemorrhage / mortality


  • Fibrinolytic Agents

Associated data