Retrospective review of thienopyridine therapy in migraineurs with patent foramen ovale

Abstract

ObjectiveWe retrospectively reviewed our clinical experience using off-label thienopyridine agents in patients with migraine headache (MHA) and patent foramen ovale (PFO).MethodsBetween 2011 and 2017, MHA/PFO patients referred to our practice were clinically treated with clopidogrel specifically for MHA. Those with ≥50% reduction in monthly MHA days compared with baseline were deemed MHA responders. MHA nonresponders with inadequate platelet inhibition by PRU testing were offered prasugrel. Thienopyridine-responsive patients were then offered PFO closure.ResultsOf 136 patients (86% female, mean age 37.9 years, mean MHA burden 14.7 days/month), 80 (59%) were MHA responders to clopidogrel. The clopidogrel responder rate was equivalent in episodic, chronic, aura, and nonaura subgroups. A total of 19/45 (40%) MHA nonresponders had inadequate platelet inhibition by PRU testing on clopidogrel. Sixteen of those patients received prasugrel, were adequately platelet inhibited by PRU, and 10/16 (62%) converted to MHA responders. A total of 56/90 thienopyridine-responsive patients underwent subsequent PFO closure with thienopyridine discontinuation after 3 months. Ninety-four percent had ongoing MHA relief. A total of 8/8 responders who stopped thienopyridine without PFO closure had resumption of MHA symptoms.ConclusionSuccessful P2Y12 platelet inhibition seemed to reduce MHA symptoms in some patients with PFO, suggesting a platelet-based mechanism/trigger. The nearly parallel response to PFO closure may mechanistically link venous platelet activation with the right-to-left shunt of PFO. Thienopyridine responsiveness could be used to enrich the study population for a new MHA/PFO trial.Classification of evidenceThis study provides Class IV evidence that in patients with PFO, P2Y12 inhibition improved MHA symptoms.

Migraine and Ischemic Stroke in Women. A Narrative Review

“…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).…”

P2Y12 receptor mediates microglial activation via RhoA/ROCK pathway in the trigeminal nucleus caudalis in a mouse model of chronic migraine

“…However, whether P2Y12R is involved in the development of CM has not yet been studied. Several clinical studies have shown that clopidogrel, a common antithrombotic drug that inhibits the activity of P2Y12R, may prevent migraine attacks [23–25]. Thus, it is reasonable to predict that P2Y12R is involved in the pathogenesis of CM.…”

A Nomogram for the Prediction of Cessation of Migraine Among Patients With Patent Foramen Ovale After Percutaneous Closure

“…A history of antiplatelet also found contributed to the relief of migraine. For example, a previous study had reported clopidogrel, a thienopyridine platelet P2Y12 receptor inhibitor, could reduce migraine headache symptoms in certain patients with PFO, which demonstrating a platelet-based mechanism/trigger (39). Clopidogrel may have a primary prophylactic role in migraine patients, and could contribute to select patients who would benefit from PFO closure (40).…”