title: Meta-analysis of intracranial hemorrhage in acute coronary syndromes: incidence, predictors, and clinical outcomes.
abstract: 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.
  
  
  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.
  
  
  BACKGROUND
  URL: https://www.clinicaltrials.gov/. Unique identifiers: TRACER: NCT00527943, PLATO: NCT00391872, APPRAISE-2: NCT00831441, TRILOGY ACS: NCT00699998.
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA (K.W.M., R.A.H.).
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Duke Clinical Research Institute, Durham, NC (R.H., D.W., J.H.A., P.T., R.D.L., M.O., M.T.R.).
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hager
authors.affiliation: Duke Clinical Research Institute, Durham, NC (R.H., D.W., J.H.A., P.T., R.D.L., M.O., M.T.R.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Wojdyla
authors.affiliation: Green Lane Cardiovascular Service, Auckland, New Zealand (H.D.W.).
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.affiliation: Division of Cardiology, University of Alberta, Edmonton, Canada (P.W.A.).
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.affiliation: Duke Clinical Research Institute, Durham, NC (R.H., D.W., J.H.A., P.T., R.D.L., M.O., M.T.R.).
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.affiliation: Duke Clinical Research Institute, Durham, NC (R.H., D.W., J.H.A., P.T., R.D.L., M.O., M.T.R.).
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tricoci
authors.affiliation: Duke Clinical Research Institute, Durham, NC (R.H., D.W., J.H.A., P.T., R.D.L., M.O., M.T.R.).
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: Duke Clinical Research Institute, Durham, NC (R.H., D.W., J.H.A., P.T., R.D.L., M.O., M.T.R.).
authors.forename: E Magnus
authors.initials: EM
authors.lastname: Ohman
authors.affiliation: Duke Clinical Research Institute, Durham, NC (R.H., D.W., J.H.A., P.T., R.D.L., M.O., M.T.R.).
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Roe
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA (K.W.M., R.A.H.).
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.affiliation: Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden (L.W.).
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications*; D000367:Age Factors; D000368:Aged; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000209:etiology / Q000401:mortality; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects; D006801:Humans; D006973:Hypertension / Q000150:complications; D015994:Incidence; D020300:Intracranial Hemorrhages / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013345:Subarachnoid Hemorrhage / Q000453:epidemiology / Q000209:etiology / Q000401:mortality
chemical_list: D005343:Fibrinolytic Agents
keywords: acute coronary syndromes; clinical outcomes; intracranial hemorrhage; systematic review