title: Risk of intracranial haemorrhage with bolus versus infusion thrombolytic therapy: a meta-analysis.
abstract: BACKGROUND
  Although thrombolytic therapy given by bolus injection seems to be as effective as infusion over 60-90 min, no single trial has been adequately powered to detect clinically important safety differences between the two strategies. We did a meta-analysis to find out whether bolus administration of thrombolytics is associated with an increased frequency of intracranial haemorrhage.
  
  
  METHODS
  We identified randomised trials comparing bolus with infusion thrombolytic therapy by a search of electronic databases, reference lists, and conference proceedings. Odds ratios for primary intracranial haemorrhage, non-haemorrhagic stroke, mortality, and reinfarction were calculated for each trial and were combined in a fixed-effects model.
  
  
  RESULTS
  Seven trials, involving a total of 103,972 patients, met our inclusion criteria. Bolus treatment was associated with an increased risk of intracranial haemorrhage compared with infusion (0.8 vs 0.6%; odds ratio 1.25 [95% CI 1.08-1.45]; p=0.003). The increased risk was most striking in trials comparing bolus with infusion administration of the same agent (1.75 [1.32-2.33], p=0.0001), but was also evident in trials comparing a newer-generation bolus agent with standard infusion therapy (1.25 [1.03-1.50]; p=0.02). The rates of non-haemorrhagic stroke (0.94 [0.81-1.09]), 30-day mortality (1.01 [0.97-1.06]), or reinfarction (1.04 [0.97-1.11]) did not differ between the two strategies.
  
  
  CONCLUSIONS
  The increased risk of bolus thrombolytic treatment seems to be primarily associated with the method of administration rather than properties of the agents. Although the increased risk of intracranial haemorrhage is small, physicians should balance this risk against the putative benefits of easier administration with no difference in mortality or reinfarction.
authors.affiliation: Division of Cardiology, and the Population Health Institute, Hamilton Health Sciences Corporation, McMaster University, Canada.
authors.forename: S R
authors.initials: SR
authors.lastname: Mehta
authors.forename: J W
authors.initials: JW
authors.lastname: Eikelboom
authors.forename: S
authors.initials: S
authors.lastname: Yusuf
mesh_terms: D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D020300:Intracranial Hemorrhages / Q000209:etiology*; D009203:Myocardial Infarction / Q000188:drug therapy*; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D015912:Thrombolytic Therapy / Q000009:adverse effects* / Q000379:methods*
chemical_list: D005343:Fibrinolytic Agents