title: Targeted use of heparin, heparinoids, or low-molecular-weight heparin to improve outcome after acute ischaemic stroke: an individual patient data meta-analysis of randomised controlled trials.
abstract: BACKGROUND
  Many international guidelines on the prevention of venous thromboembolism recommend targeting heparin treatment at patients with stroke who have a high risk of venous thrombotic events or a low risk of haemorrhagic events. We sought to identify reliable methods to target anticoagulant treatment and so improve the chance of avoiding death or dependence after stroke.
  
  
  METHODS
  We obtained individual patient data from the five largest randomised controlled trials in acute ischaemic stroke that compared heparins (unfractionated heparin, heparinoids, or low-molecular-weight heparin) with aspirin or placebo. We developed and evaluated statistical models for the prediction of thrombotic events (myocardial infarction, stroke, deep vein thrombosis, or pulmonary embolism) and haemorrhagic events (symptomatic intracranial or significant extracranial) in the first 14 days after stroke. We calculated the absolute risk difference for the outcome "dead or dependent" in patients grouped by quartiles of predicted risk of thrombotic and haemorrhagic events with random effect meta-analysis.
  
  
  RESULTS
  Patients with ischaemic stroke who were of advanced age, had increased neurological impairment, or had atrial fibrillation had a high risk of both thrombotic and haemorrhagic events after stroke. Additionally, patients with CT-visible evidence of recent cerebral ischaemia were at increased risk of thrombotic events. In evaluation datasets, the area under a receiver operating curve for prediction models for thrombotic events was 0·63 (95% CI 0·59-0·67) and for haemorrhagic events was 0·60 (0·55-0·64). We found no evidence that the net benefit from heparins increased with either increasing risk of thrombotic events or decreasing risk of haemorrhagic events.
  
  
  CONCLUSIONS
  There was no evidence that patients with ischaemic stroke who were at higher risk of thrombotic events or lower risk of haemorrhagic events benefited from heparins. We were therefore unable to define a targeted approach to select the patients who would benefit from treatment with early anticoagulant therapy. We recommend that guidelines for routine or selective use of heparin in stroke should be revised.
  
  
  BACKGROUND
  MRC.
authors: Division of Clinical Neurosciences, University of Edinburgh, Bramwell Dott Building, Western General Hospital, Edinburgh, UK. william.whiteley@ed.ac.uk
authors: William N
authors: WN
authors: Whiteley
authors: Harold P
authors: HP
authors: Adams
authors: Philip M W
authors: PM
authors: Bath
authors: Eivind
authors: E
authors: Berge
authors: Per Morten
authors: PM
authors: Sandset
authors: Martin
authors: M
authors: Dennis
authors: Gordon D
authors: GD
authors: Murray
authors: Ka-Sing Lawrence
authors: KS
authors: Wong
authors: Peter A G
authors: PA
authors: Sandercock
mesh_terms: D002545:Brain Ischemia / Q000188:drug therapy* / Q000453:epidemiology; D016503:Drug Delivery Systems / Q000379:methods*; D006493:Heparin / Q000008:administration & dosage; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006496:Heparinoids / Q000008:administration & dosage*; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D020521:Stroke / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D006495:Heparin, Low-Molecular-Weight; D006496:Heparinoids; D006493:Heparin
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