title: Timing of vitamin K antagonist re-initiation following intracranial hemorrhage in mechanical heart valves: Systematic review and meta-analysis.
abstract: BACKGROUND
  While evidence supports resumption of vitamin K antagonists (VKAs) among mechanical heart valve (MHV) patients presenting with anticoagulant-associated intracranial hemorrhage (ICH), ideal timing of resumption is uncertain.
  
  
  OBJECTIVE
  To determine the optimal timing of VKA re-initiation and its associated clinical outcomes.
  
  
  METHODS
  We performed a systematic review and a meta-analysis of studies published from January 1950 to August 2015. We extracted data on the location of initial ICH, use of cranial surgery, presence of atrial fibrillation, MHV type and position, number of MHVs, and timing of VKA resumption. Outcomes including valve thrombosis, thromboembolic events or ICH recurrence were recorded. Meta-regression analysis was conducting with controlling for covariates. We calculated absolute risks, and assessed the effect of anticoagulant resumption timing on ICH recurrence.
  
  
  RESULTS
  23 case-series and case-reports were identified. Overall ICH recurrence was 13% (95% confidence interval [CI], 7%-25%), while valve thrombosis and ischemic strokes occurred at 7% (95% CI, 3%-17%) and 12% (95% CI, 5%-23%) respectively. A trend towards lower ICH recurrence was observed with delayed VKA resumption (slope estimate -0.2154, p=0.10). Recurrence rate ranged from 50% with VKA resumption at 3days to 0% with resumption at 16days.
  
  
  CONCLUSIONS
  Among patients with MHV, there is inadequate data to suggest an optimal timing of VKA re-initiation following an ICH, though delayed restart appears to be protective against recurrence but is associated with higher risk of thrombosis. Our analysis suggests 4-7days might be an ideal time with least risk of thrombosis or ICH recurrence.
authors.affiliation: Division of Neurosurgery, Department of Surgery, University of Ottawa, Ottawa, Canada; Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada. Electronic address: falkherayf@toh.ca.
authors.forename: Fahad
authors.initials: F
authors.lastname: AlKherayf
authors.affiliation: School of Medicine, Queen's University, Kingston, Canada.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: Esteban
authors.initials: E
authors.lastname: Gandara
authors.affiliation: Division of Neurosurgery, Department of Surgery, Hôpital du Sacré-Coeur de Montréal, Montreal, Canada.
authors.forename: Harrison
authors.initials: H
authors.lastname: Westwick
authors.affiliation: Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Ioana Doina
authors.initials: ID
authors.lastname: Moldovan
authors.affiliation: Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada; Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Wells
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D006350:Heart Valve Prosthesis / Q000009:adverse effects*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced*; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin
keywords: Anticoagulant; Intracranial hemorrhage; Mechanical valve; Warfarin