Ticagrelor for Refractory Migraine/Patent Foramen Ovale (TRACTOR)

Reisman, Adam; Robbins, Barbara T.; Chou, Denise E.; Yugrakh, Marianna Shnayderman; Gross, Giti J.; Privitera, Lauren; Nazif, Tamim; Sommer, Robert J.

doi:10.1212/wnl.0000000000006573

Cited by 28 publications

(20 citation statements)

References 13 publications

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“…Although not recommended for migraine prophylaxis in current headache guidelines, 173 antiplatelet medications (aspirin and thienopyridines, clopidogrel, and ticagrelor) have been studied in persons with migraine, including in those with PFO or who are status post closure procedures (Table 3). 174‐181 Given the paucity of randomized controlled trials (RCT) and the inconsistency of results, additional research, especially in persons with MWA and PFO, is indicated. The 3 RCT of percutaneous PFO closure in persons with migraine (MIST, 182 PRIMA, 183 and PREMIUM 184 ) failed to meet their primary endpoints, which differed between the trials (Table 4).…”

Section: Mechanistic Implications Of Clinical Trialsmentioning

confidence: 99%

Migraine and Ischemic Stroke in Women. A Narrative Review

Tietjen

Maly

2020

Headache

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Objective/Background.-Migraine is associated with ischemic stroke. Women are 3-fold as likely as men to have migraine, and high estrogen states increase the risk of migraine with aura (MWA), venous thromboembolism (VTE), and of stroke. We review the epidemiological and mechanistic evidence of the migraine-stroke relationship and its risk factors, with a focus on women and conditions that exclusively or predominantly affect them.Methods.-We performed a search of MEDLINE/PubMed database, then a narrative review of the epidemiological evidence of the migraine-stroke relationship as well as the evidence for arterial, thrombophilic, and cardiac mechanisms to explain this connection. We examine the implications of this evidence for the diagnostic evaluation and treatment of MWA.Results.-MWA is associated with multiple stroke risk factors, such as hypertension, hyperlipidemia, diabetes mellitus, cigarette smoking, atrial fibrillation, and patent foramen ovale. In women, MWA is also associated with biomarkers of endothelial activation, hormonal contraceptive use, pregnancy, and VTE. This suggests that a subset of auras may be secondary, that is, induced by ischemia related to microemboli or in situ thrombosis. MWA-associated ischemic stroke is more common in young (<45 years old) women with high frequency of migraine attacks, hormonal contraception use, and with pregnancy and preeclampsia. There is increasing evidence that cardioembolism, often in conjunction with thrombophilia, plays a prominent role in MWA-associated cerebral infarction.Conclusion.-The commonality of factors associated with MWA and with MWA-associated stroke suggest that persons with secondary, ischemia-induced aura may be at elevated risk of stroke. Although further research is needed, we recommend consideration of a diagnostic evaluation of MWA that mirrors the evaluation of transient ischemic attack, given that prophylactic treatment targeting the ischemic origin of secondary aura may prevent migraine as well as stroke.

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Section: Mechanistic Implications Of Clinical Trialsmentioning

confidence: 99%

Migraine and Ischemic Stroke in Women. A Narrative Review

Tietjen

Maly

2020

Headache

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“…Serotonin causes both vasodilation and vasoconstriction in different concentrations, and can thereby be among the triggers of a migraine. Migraine has also been related to cerebral embolisms, and supports the theory of both platelet activation and shear stress induced by the embolism, as well as micro embolisms through the shunt as an independent activator of migraine, and platelet inhibitors have shown good results in symptom reduction in migraine patients with PFO 5–8 .…”

Section: Introductionmentioning

confidence: 55%

The Burden of Migraine in Adults with Atrial Septal Defect: A Nationwide Cohort Study

Nyboe

Nymann

Ovesen

et al. 2019

Sci Rep

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We aimed to investigate migraine diagnoses in a hospital setting, use of prescription migraine medicine and levels of serotonin in patients with atrial septal defect. Using Danish national registries to identify all patients born before 1994 diagnosed with atrial septal defect between 1959 and 2013, thus including 2277 patients and a gender and age matched comparison cohort of 22756. Plasma serotonin was measured in 136 patients with a small, unclosed, atrial septal defects and 18 controls. Patients with atrial septal defect had an increased risk of receiving a migraine diagnosis (HR 3.4 (95% CI: 2.6–4.6)) and receiving migraine medicine (HR 1.8 (95% CI: 1.2–2.5)). Ten years after closure, 93% of those using migraine medicine pre-closure, were still receiving this. The risk of having very high plasma serotonin levels was increased in patients with atrial septal defect compared with the control group, but there was no difference in the median values between the two groups. Migraine and use of migraine medicine were increased in atrial septal defect patients. The use of medicine was not diminished by closure of the defect. Plasma serotonin was severely elevated in 18% of the patients with atrial septal defect.

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“…After applying the inclusion criteria, four studies for a total of 262 migraine patients with or without PFO ( Table 1 ) and three studies involving 539 patients with antiplatelet treatment for the prevention of new-onset migraine attacks following ASDC ( Table 2 ) were included. These studies consisted of two RCTs [ 9 , 14 ], three open-label single-arm feasibility studies [ 10 – 12 ], and two retrospective observational studies [ 13 , 15 ]. Both of the two RCTs were scored at 7 using the Jadad scoring system (Supplemental Table 1 ), suggesting high quality.…”

Section: Resultsmentioning

confidence: 99%

“…The primary outcomes were headache responder rate and rate of new-onset migraine attacks following ASDC. Headache responder was measured differently across the enrolled studies, including (1) those with ≥50% reduction in monthly MHA days compared with baseline [ 10 , 11 ] and (2) those with >50% reduction or complete elimination of migraine symptoms [ 12 ]. The secondary outcome was the rate of migraineurs with the ongoing benefit of the responder who underwent PFO closure, after discontinuation of P2Y12 platelet inhibitors.…”

Section: Methodsmentioning

confidence: 99%

Platelet P2Y12 Inhibitor in the Treatment and Prevention of Migraine: A Systematic Review and Meta-Analysis

Wang

Cao

Liu

et al. 2022

Behavioural Neurology

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There have been speculation and research linking migraine with abnormalities of platelet aggregation and activation. The role of the P2Y12 platelet inhibitor in the treatment of migraine has not been established. We aim to evaluate the efficacy of the platelet P2Y12 inhibitor in the treatment of migraine and prevention of new-onset migraine headache (MHA) following transcatheter atrial septal defect closure (ASDC). We searched the PubMed, Web of Science, and Cochrane Library databases for relevant studies. The primary outcomes were the headache responder rate and the rate of new-onset migraine attacks following ASDC. Four studies for a total of 262 migraine patients with or without patent foramen ovale (PFO) and three studies involving 539 patients with antiplatelet treatment in the prevention of new-onset migraine following ASDC were included. The pooled responder rate of the P2Y12 inhibitor for migraine was 0.64 (95% CI: 0.43 to 0.81). For patients who underwent ASDC, the use of antiplatelet regimens including the P2Y12 inhibitor, compared with regimens excluding P2Y12 inhibitor, resulted in a lower rate of new-onset migraine (OR: 0.41, 95% CI: 0.22 to 0.77, P = 0.005 ). We concluded that the P2Y12 platelet inhibitor may have a primary prophylactic role in migraine patients with or without PFO and prevent new-onset MHA after ASDC. The responsiveness of the P2Y12 inhibitor could help select candidates who would benefit from PFO closure. It warrants further large-scale research to explore the role of the P2Y12 inhibitor, particularly in a proportion of migraine patients.

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Ticagrelor for Refractory Migraine/Patent Foramen Ovale (TRACTOR)

Cited by 28 publications

References 13 publications

Migraine and Ischemic Stroke in Women. A Narrative Review

Migraine and Ischemic Stroke in Women. A Narrative Review

The Burden of Migraine in Adults with Atrial Septal Defect: A Nationwide Cohort Study

Platelet P2Y12 Inhibitor in the Treatment and Prevention of Migraine: A Systematic Review and Meta-Analysis

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