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

Abstract

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Horlick reports grants from Hospital Laval during the conduct of the study; grants and personal fees from St. Jude Medical, Medtronic, and Edwards Lifesciences outside the submitted work; and serves on the medical advisory board of RealView Imaging outside the submitted work. Dr Ibrahim reports grants, personal fees, and other support from Abbott Laboratories and Boston Scientific and personal fees from Edwards Lifesciences, Medtronic, Cardia, and Occlutech outside the submitted work. Dr Rodés-Cabau reports grants from St. Jude Medical and Sanofi during the conduct of the study and holds the Research Chair of Fondation Famille Jacques Larivière for the Development of Structural Heart Disease Interventions. No other disclosures were reported.

Figures

Figure.. Flowchart of Recruitment, Treatment Allocation, and Follow-up of the Clopidogrel for the Prevention of New Onset Migraine Headache Following Transcatheter Closure of Atrial Septal Defects (CANOA) Study

ASD indicates atrial septal defect.