Effect of Clopidogrel and Aspirin vs Aspirin Alone on Migraine Headaches After Transcatheter Atrial Septal Defect Closure
Authors: Jérôme Wintzer-Wehekind, Eric Horlick, Reda Ibrahim, Asim N. Cheema, Marino Labinaz, Najaf Nadeem, Mark Osten, Mélanie Côté, Josep Ramon Marsal, Donald Rivest, Alier Marrero, Christine Houde, Josep Rodés-Cabau
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> 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. <h3>Objective</h3> To assess the incidence of migraine attacks at 6- and 12-month follow-up after transcatheter ASD closure. <h3>Design, Setting, and Participants</h3> 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. <h3>Interventions</h3> 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. <h3>Main Outcomes and Measures</h3> Incidence and severity of migraine attacks at 6- and 12-month follow-up. <h3>Results</h3> 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;<i>P</i> = .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:<i>P</i> &lt; .001). The severity of migraine attacks progressively decreased over time; no moderate or severe attacks occurred at 6 and 12 months (vs 3 months:<i>P</i> &lt; .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%];<i>P</i> = .28) and 12 months (initial clopidogrel group: 3 of 84 [3.6%]; initial placebo group: 1 of 87 [1.1%];<i>P</i> = .36) after ASD closure. Only 2 patients (1.2%; 1 patient per group) presented with new-onset migraine attacks after 3 months. <h3>Conclusions and Relevance</h3> 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. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT00799045