title: Effect of Clopidogrel and Aspirin vs Aspirin Alone on Migraine Headaches After Transcatheter Atrial Septal Defect Closure: The CANOA Randomized Clinical Trial.
abstract: OBJECTIVE
  The occurrence of new-onset migraine attacks is a complication of transcatheter atrial septal defect (ASD) closure. It has been suggested that clopidogrel may reduce migraine attacks after ASD closure.
  
  
  OBJECTIVE
  To assess the efficacy of clopidogrel, used in addition to taking aspirin, for the prevention of migraine attacks following ASD closure.
  
  
  METHODS
  Randomized, double-blind clinical trial performed in 6 university hospitals in Canada. Participants were 171 patients with an indication for ASD closure and no history of migraine.
  
  
  METHODS
  Patients were randomized (1:1) to receive dual antiplatelet therapy (aspirin + clopidogrel [the clopidogrel group], n = 84) vs single antiplatelet therapy (aspirin + placebo [the placebo group], n = 87) for 3 months following transcatheter ASD closure. The first patient was enrolled in December 2008, and the last follow-up was completed in February 2015.
  
  
  METHODS
  The primary efficacy outcome was the monthly number of migraine days within the 3 months following ASD closure in the entire study population. The incidence and severity of new-onset migraine attacks, as evaluated by the Migraine Disability Assessment questionnaire, were prespecified secondary end points. A zero-inflated Poisson regression model was used for data analysis.
  
  
  RESULTS
  The mean (SD) age of the participants was 49 (15) years and 62% (106) were women. Patients in the clopidogrel group had a reduced mean (SD) number of monthly migraine days within the 3 months following the procedure (0.4 [95% CI, 0.07 to 0.69] days) vs the placebo group (1.4 [95% CI, 0.54 to 2.26] days; difference, -1.02 days [95% CI, -1.94 to -0.10 days]; incident risk ratio [IRR], 0.61 [95% CI, 0.41 to 0.91]; P = .04) and a lower incidence of migraine attacks following ASD closure (9.5% for the clopidogrel group vs 21.8% for the placebo group; difference, -12.3% [95% CI, -23% to -1.6%]; odds ratio [OR], 0.38 [95% CI, 0.15 to 0.89]; P = .03). Among patients with migraines, those in the clopidogrel group had less-severe migraine attacks (zero patients with moderately or severely disabling migraine attacks vs 37% [7 patients] in the placebo group; difference, -36.8% [95% CI, -58.5% to -15.2%]; P = .046). There were no between-group differences in the rate of patients with at least 1 adverse event (16.7% [14 patients] in the clopidogrel group vs 21.8% [19 patients] in the placebo group; difference, -5.2% [95% CI, -17% to 6.6%]; P = .44).
  
  
  CONCLUSIONS
  Among patients who underwent transcatheter ASD closure, the use of clopidogrel and aspirin, compared with aspirin alone, resulted in a lower monthly frequency of migraine attacks over 3 months. Further studies are needed to assess generalizability and durability of this effect.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00799045.
authors.affiliation: Department of Cardiology, Quebec Heart and Lung Institute, Quebec City, Quebec, Canada.
authors.forename: Josep
authors.initials: J
authors.lastname: Rodés-Cabau
authors.affiliation: Department of Cardiology, Toronto General Hospital, Toronto, Ontario, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Horlick
authors.affiliation: Department of Cardiology, Montreal Heart Institute, Montreal, Quebec, Canada.
authors.forename: Reda
authors.initials: R
authors.lastname: Ibrahim
authors.affiliation: Department of Cardiology, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Asim N
authors.initials: AN
authors.lastname: Cheema
authors.affiliation: Department of Cardiology, Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Marino
authors.initials: M
authors.lastname: Labinaz
authors.affiliation: Department of Cardiology, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
authors.forename: Najaf
authors.initials: N
authors.lastname: Nadeem
authors.affiliation: Department of Cardiology, Toronto General Hospital, Toronto, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Osten
authors.affiliation: Department of Cardiology, Quebec Heart and Lung Institute, Quebec City, Quebec, Canada.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Côté
authors.affiliation: Epidemiology Unit of the Cardiology Department, Vall d'Hebron Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Josep Ramon
authors.initials: JR
authors.lastname: Marsal
authors.affiliation: Department of Neurology, Hôtel Dieu de Lévis, Quebec City, Quebec, Canada.
authors.forename: Donald
authors.initials: D
authors.lastname: Rivest
authors.affiliation: Department of Neurology, Centre Hospitalier Universitaire Georges. L Dumont, Moncton, New Brunswick, Canada.
authors.forename: Alier
authors.initials: A
authors.lastname: Marrero
authors.affiliation: Department of Pediatric Cardiology, Centre Hospitalier Universitaire de Québec, Quebec City, Quebec, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Houde
mesh_terms: D001241:Aspirin / Q000008:administration & dosage*; D006328:Cardiac Catheterization / Q000009:adverse effects* / Q000379:methods; D006348:Cardiac Surgical Procedures / Q000009:adverse effects* / Q000379:methods; D000077144:Clopidogrel; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D051271:Headache Disorders, Secondary / Q000188:drug therapy* / Q000209:etiology; D006344:Heart Septal Defects, Atrial / Q000601:surgery*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy* / Q000209:etiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D012044:Regression Analysis; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin