title: Effects of blood pressure lowering on intracranial and extracranial bleeding in patients on antithrombotic therapy: the PROGRESS trial.
abstract: OBJECTIVE
  Observational studies demonstrate strong associations between blood pressure and bleeding complications of antithrombotic therapy. The objective was to determine whether blood pressure lowering reduces risks of bleeding in patients on antithrombotic therapy.
  
  
  METHODS
  This is a subsidiary analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) trial, a randomized, placebo-controlled trial. A total of 6105 patients with cerebrovascular disease were randomly assigned to either active treatment (perindopril ± indapamide) or placebo(s). The outcomes were intracranial and extracranial bleeding.
  
  
  RESULTS
  There were 4876 (80%) patients on antithrombotic therapy at baseline. Over a mean follow-up of 3.9 years, 119 intracranial and 123 extracranial bleeding events were observed. Among patients with and without antithrombotic therapy, active treatment lowered blood pressure by 8.9/4.0 and 9.3/3.8 mm Hg and reduced the risks of intracranial bleeding by 46% (95% CI, 7%-69%) and 70% (39%-85%), respectively. However, active treatment did not reduce the risks of extracranial bleeding significantly in either group. Among patients on antithrombotic therapy, the lowest risk of intracranial bleeding was observed in participants with the lowest follow-up systolic blood pressure levels (median, 113 mm Hg).
  
  
  CONCLUSIONS
  Blood pressure lowering provides protection against intracranial bleeding among patients with cerebrovascular disease including those receiving antithrombotic therapy.
authors.affiliation: George Institute for Global Health, PO Box M201, Missenden Road, NSW 2050 Australia.
authors.forename: Hisatomi
authors.initials: H
authors.lastname: Arima
authors.forename: Craig
authors.initials: C
authors.lastname: Anderson
authors.forename: Teruo
authors.initials: T
authors.lastname: Omae
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.forename: Stephen
authors.initials: S
authors.lastname: MacMahon
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancia
authors.forename: Marie-Germaine
authors.initials: MG
authors.lastname: Bousser
authors.forename: Christophe
authors.initials: C
authors.lastname: Tzourio
authors.forename: Anthony
authors.initials: A
authors.lastname: Rodgers
authors.forename: Bruce
authors.initials: B
authors.lastname: Neal
authors.forename: John
authors.initials: J
authors.lastname: Chalmers
mesh_terms: D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D020300:Intracranial Hemorrhages / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D020913:Perindopril / Q000008:administration & dosage*; D012307:Risk Factors; D020521:Stroke / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D005343:Fibrinolytic Agents; D020913:Perindopril