title: Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial.
abstract: OBJECTIVE
  The purpose of this study was to determine the possible benefit of dual antiplatelet therapy in patients with prior myocardial infarction (MI), ischemic stroke, or symptomatic peripheral arterial disease (PAD).
  
  
  BACKGROUND
  Dual antiplatelet therapy with clopidogrel plus aspirin has been validated in the settings of acute coronary syndromes and coronary stenting. The value of this combination was recently evaluated in the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial, where no statistically significant benefit was found in the overall broad population of stable patients studied.
  
  
  METHODS
  We identified the subgroup in the CHARISMA trial who were enrolled with documented prior MI, ischemic stroke, or symptomatic PAD.
  
  
  RESULTS
  A total of 9,478 patients met the inclusion criteria for this analysis. The median duration of follow-up was 27.6 months. The rate of cardiovascular death, MI, or stroke was significantly lower in the clopidogrel plus aspirin arm than in the placebo plus aspirin arm: 7.3% versus 8.8% (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01). Additionally, hospitalizations for ischemia were significantly decreased, 11.4% versus 13.2% (HR 0.86, 95% CI 0.76 to 0.96, p = 0.008). There was no significant difference in the rate of severe bleeding: 1.7% versus 1.5% (HR 1.12, 95% CI 0.81 to 1.53, p = 0.50); moderate bleeding was significantly increased: 2.0% versus 1.3% (HR 1.60, 95% CI 1.16 to 2.20, p = 0.004).
  
  
  CONCLUSIONS
  In this analysis of the CHARISMA trial, the large number of patients with documented prior MI, ischemic stroke, or symptomatic PAD appeared to derive significant benefit from dual antiplatelet therapy with clopidogrel plus aspirin. Such patients may benefit from intensification of antithrombotic therapy beyond aspirin alone, a concept that future trials will need to validate. (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA]; http://clinicaltrials.gov/ct/show/NCT00050817?order=1; NCT00050817).
authors.affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA. bhattd@ccf.org
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Flather
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
authors.forename: Peter B
authors.initials: PB
authors.lastname: Berger
authors.forename: Henry R
authors.initials: HR
authors.lastname: Black
authors.forename: William E
authors.initials: WE
authors.lastname: Boden
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
authors.forename: Eric A
authors.initials: EA
authors.lastname: Cohen
authors.forename: Mark A
authors.initials: MA
authors.lastname: Creager
authors.forename: J Donald
authors.initials: JD
authors.lastname: Easton
authors.forename: Christian W
authors.initials: CW
authors.lastname: Hamm
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: S Claiborne
authors.initials: SC
authors.lastname: Johnston
authors.forename: Koon-Hou
authors.initials: KH
authors.lastname: Mak
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mas
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Pearson
authors.forename: P Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Steven R
authors.initials: SR
authors.lastname: Steinhubl
authors.forename: Michael A
authors.initials: MA
authors.lastname: Weber
authors.forename: Liz
authors.initials: L
authors.lastname: Fabry-Ribaudo
authors.forename: Tingfei
authors.initials: T
authors.lastname: Hu
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D000077144:Clopidogrel; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D016491:Peripheral Vascular Diseases / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D020521:Stroke / Q000188:drug therapy*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin