title: The Japanese aggrenox (extended-release dipyridamole plus aspirin) stroke prevention versus aspirin programme (JASAP) study: a randomized, double-blind, controlled trial.
abstract: BACKGROUND
  Despite improvements in treatment, stroke still carries a high death toll and disability in Asia. Extended-release dipyridamole (ER-DP) plus acetylsalicylic acid (ASA) has consistently been shown to be superior over conventional platelet inhibition by ASA. ER-DP plus ASA is well established in the secondary prevention of stroke in a lot of countries including the USA and Europe. DP has an established benefit in the treatment of heart disease in Japan; however, for the prevention of stroke, the fixed-dose combination of ER-DP plus ASA has only been investigated in a small number of patients in Japan.
  
  
  METHODS
  The aim of this double-blind, randomized clinical trial was to investigate the efficacy and safety of ER-DP plus ASA versus 81 mg ASA over 1 year. The primary end point of this study was the event rate of recurrent ischemic stroke (fatal or nonfatal) using the Kaplan-Meier method and Cox regression analysis.
  
  
  RESULTS
  Of the 1,294 enrolled patients, the primary end point was analyzed in 652 patients in the ER-DP plus ASA group and 639 in the ASA group. The incidence of ischemic stroke was 6.9% for ER-DP plus ASA and 5.0% for ASA with a hazard ratio of 1.47 (95% confidence interval 0.93-2.31) for the primary end point. The ASA treatment group was found to have a lower than expected yearly event rate, compared to other studies in Japanese stroke patients. Noninferiority of ER-DP plus ASA versus ASA could not be shown. The risks of major bleeding events and intracranial hemorrhage were found to be similar between the treatment arms. There were 4 deaths (0.6%) in the ER-DP plus ASA group and 10 (1.6%) in the ASA group.
  
  
  CONCLUSIONS
  The results of the study are inconclusive. Noninferiority of ER-DP plus ASA versus ASA could not be established, a difference between treatments could not be shown for the primary end point. Possible reasons for this result include a small sample size, low event rates and too short a treatment duration (ClinicalTrials. gov number, NCT00311402).
authors.affiliation: Department of Neurology, Tokyo Women's Medical University, Japan. suchiyam@nij.twmu.ac.jp
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Uchiyama
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Urano
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Horie
authors.forename: Takenori
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D000368:Aged; D044466:Asian People / Q000706:statistics & numerical data; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D000068342:Aspirin, Dipyridamole Drug Combination; D002545:Brain Ischemia / Q000208:ethnology / Q000401:mortality / Q000517:prevention & control*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D004176:Dipyridamole / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models; D020521:Stroke / Q000208:ethnology / Q000401:mortality / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000068342:Aspirin, Dipyridamole Drug Combination; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D001241:Aspirin