title: Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage.
abstract: BACKGROUND
  Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. Rebleeding is probably related to dissolution of the blood clot at the site of aneurysm rupture by natural fibrinolytic activity. This review is an update of a previously published Cochrane review.
  
  
  OBJECTIVE
  To assess the effects of antifibrinolytic treatment in people with aneurysmal subarachnoid haemorrhage.
  
  
  METHODS
  We searched the Cochrane Stroke Group Trials Register (February 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE (1948 to December 2012), and EMBASE (1947 to December 2012). In an effort to identify further published, unpublished, and ongoing studies we searched reference lists and trial registers, performed forward tracking of relevant references and contacted drug companies.
  
  
  METHODS
  Randomised trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid, epsilon amino-caproic acid, or an equivalent) with control in people with subarachnoid haemorrhage of suspected or proven aneurysmal cause.
  
  
  METHODS
  Two review authors independently selected trials for inclusion and extracted the data. Three review authors assessed trial quality. For the primary outcome we converted the outcome scales between good and poor outcome for the analysis. We scored death from any cause and rates of rebleeding, cerebral ischaemia, and hydrocephalus per treatment group. We expressed effects as risk ratios (RR) with 95% confidence intervals (CI). We used random-effects models for all analyses.
  
  
  RESULTS
  We included 10 trials involving 1904 participants. The risk of bias was low in six studies. Four studies were open label and were rated as high risk of performance bias. One of these studies was also rated as high risk for attrition bias. Four trials reported on poor outcome (death, vegetative state, or severe disability) with a pooled risk ratio (RR) of 1.02 (95% confidence interval (CI) 0.91 to 1.15). All trials reported on death from all causes with a pooled RR of 1.00 (95% CI 0.85 to 1.18). In a trial that combined short-term antifibrinolytic treatment (< 72 hours) with preventative measures for cerebral ischaemia the RR for poor outcome was 0.85 (95% CI 0.64 to 1.14). Antifibrinolytic treatment reduced the risk of re-bleeding reported at the end of follow-up (RR 0.65, 95% CI 0.44 to 0.97; 78 per 1000 participants), but there was heterogeneity (I² = 62%) between the trials. The pooled RR for reported cerebral ischaemia was 1.41 (95% CI 1.04 to 1.91, 83 per 1000 participants), again with heterogeneity between the trials (I² = 52%). Antifibrinolytic treatment showed no effect on the reported rate of hydrocephalus in five trials (RR 1.11, 95% CI 0.90 to 1.36).
  
  
  CONCLUSIONS
  The current evidence does not support the use of antifibrinolytic drugs in the treatment of people with aneurysmal subarachnoid haemorrhage, even in those who have concomitant treatment strategies to prevent cerebral ischaemia. Results on short-term treatment are promising, but not conclusive. Further randomised trials evaluating short-term antifibrinolytic treatment are needed to evaluate its effectiveness.
authors.affiliation: Department of Neurology, Academic Medical Centre, University of Amsterdam, PO Box 22660, Amsterdam, Netherlands, 1100 DD.
authors.forename: Merih I
authors.initials: MI
authors.lastname: Baharoglu
authors.forename: Menno R
authors.initials: MR
authors.lastname: Germans
authors.forename: Gabriel J E
authors.initials: GJ
authors.lastname: Rinkel
authors.forename: Ale
authors.initials: A
authors.lastname: Algra
authors.forename: Marinus
authors.initials: M
authors.lastname: Vermeulen
authors.forename: Jan
authors.initials: J
authors.lastname: van Gijn
authors.forename: Yvo B W E M
authors.initials: YB
authors.lastname: Roos
mesh_terms: D000284:Administration, Oral; D015119:Aminocaproic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000139:chemically induced; D016001:Confidence Intervals; D006801:Humans; D007275:Injections, Intravenous; D002532:Intracranial Aneurysm / Q000150:complications; D016032:Randomized Controlled Trials as Topic; D055502:Secondary Prevention; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000517:prevention & control; D014148:Tranexamic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid; D015119:Aminocaproic Acid