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Brief Report
September 23, 2020

Effect of Clopidogrel and Aspirin vs Aspirin Alone on Migraine Headaches After Transcatheter Atrial Septal Defect Closure: One-Year Results of the CANOA Randomized Clinical Trial

Author Affiliations
  • 1Department of Cardiology, Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada
  • 2Department of Cardiology, Toronto General Hospital, Toronto, Ontario, Canada
  • 3Department of Cardiology, Montreal Heart Institute, Montreal, Quebec, Canada
  • 4Department of Cardiology, St Michael’s Hospital, Toronto, Ontario, Canada
  • 5Department of Cardiology, Ottawa Heart Institute, Ottawa, Ontario, Canada
  • 6Department of Cardiology, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada
  • 7Epidemiology Unit of the Cardiology Department, Vall d’Hebron Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain
  • 8Department of Neurology, Hôtel Dieu de Lévis, Quebec City, Quebec, Canada
  • 9Department of Neurology, Centre Hospitalier Universitaire Georges L. Dumont, Moncton, New Brunswick, Canada
  • 10Department of Pediatric Cardiology, Centre Hospitalier Universitaire de Québec, Quebec City, Quebec, Canada
JAMA Cardiol. 2021;6(2):209-213. doi:10.1001/jamacardio.2020.4297
Key Points

Question  What is the optimal duration of clopidogrel therapy after atrial septal defect (ASD) closure to reduce the incidence of new-onset migraine attacks?

Findings  In this prespecified analysis of a randomized clinical trial of 171 patients (27 [15.8%] with new-onset migraine attacks), the occurrence and severity of migraine attacks decreased over time with a low percentage of patients with migraine attacks at 6- to 12-month follow-up and only 1% of patients with new-onset migraine attacks after the cessation of clopidogrel at 3 months after ASD closure.

Meaning  The occurrence of new-onset migraine attacks after ASD closure is an early transient complication and resolves (within 6-12 months) in most patients.


Importance  Adding clopidogrel to aspirin for 3 months after transcatheter atrial septal defect (ASD) closure results in a lower incidence of new-onset migraine attacks. However, the outcomes at 6- to 12-month follow-up (after clopidogrel cessation at 3 months) remain largely unknown.

Objective  To assess the incidence of migraine attacks at 6- and 12-month follow-up after transcatheter ASD closure.

Design, Setting, and Participants  This prespecified analysis of a randomized, double-blind clinical trial included patients with no prior history of migraine undergoing ASD closure from 6 university hospitals in Canada from December 2008 to November 2014. Patients were followed up at 3, 6, and 12 months, and a migraine headache questionnaire was administered at each time. Analysis began June 2019.

Interventions  Patients were randomized (1:1) to receive dual antiplatelet therapy (aspirin plus clopidogrel; n = 84) vs single antiplatelet therapy (aspirin plus placebo; n = 87) for 3 months following transcatheter ASD closure. After 3 months, only single antiplatelet therapy (aspirin) was pursued.

Main Outcomes and Measures  Incidence and severity of migraine attacks at 6- and 12-month follow-up.

Results  The mean (SD) age of the study population was 38 (12) years, with 106 women (62%). A total of 27 patients (15.8%) had new-onset migraine attacks within the 3 months following ASD closure (8 of 84 [9.5%] vs 19 of 87 [21.8%] in the initial clopidogrel and placebo groups, respectively; P = .03). After cessation of clopidogrel and aspirin monotherapy, the percentage of patients with migraine attacks decreased over time, with 8 (4.7%) and 4 patients (2.3%) continuing to have migraine attacks at 6 and 12 months, respectively (vs 3 months: P < .001). The severity of migraine attacks progressively decreased over time; no moderate or severe attacks occurred at 6 and 12 months (vs 3 months: P < .001). There were no differences between groups in the rate of migraine attacks at 6 months (initial clopidogrel group: 2 of 84 [2.4%]; initial placebo group: 6 of 87 [6.9%]; P = .28) and 12 months (initial clopidogrel group: 3 of 84 [3.6%]; initial placebo group: 1 of 87 [1.1%]; P = .36) after ASD closure. Only 2 patients (1.2%; 1 patient per group) presented with new-onset migraine attacks after 3 months.

Conclusions and Relevance  New-onset migraine attacks after ASD closure improved or resolved spontaneously within 6 to 12 months in most patients. No significant rebound effect was observed after clopidogrel cessation at 3 months. These results demonstrate a low rate of migraine events beyond 3 months following transcatheter ASD closure and support the early discontinuation of clopidogrel therapy if administered.

Trial Registration  ClinicalTrials.gov Identifier: NCT00799045