Do antithrombotic drugs have a role in migraine prevention? A systematic review

Abstract

Objectives: To explore the available evidence on the role of antithrombotics as migraine preventive medication.

Background: In clinical practice, the use of antithrombotic drugs in individuals with migraine is sometimes considered, especially in the case of frequent auras, association with patent foramen ovale, or prothrombotic states. This paper systematically reviews evidence on antithrombotic agents' efficacy for migraine prevention.

Methods: We performed a systematic literature search on PubMed and Scopus including observational and interventional studies focused on antiplatelets or anticoagulants as preventive treatments for migraine. The search included studies published until June 30th, 2024. Ongoing trials on Clinicaltrials.org were also explored. Quality assessment used the Cochrane Risk of Bias 2 (RoB-2) tool for randomized controlled trials (RCTs) and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) for observational studies. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO identifier CRD42024501531).

Results: Out of 1854 records, we found 12 RCTs and 8 observational studies investigating the impact of antithrombotic drugs in migraine prevention. Due to heterogeneity of data, a meta-analysis was not feasible. RCTs tested acetylsalicylic acid (ASA) alone (seven), ASA in combination with other preventive treatments (two), clopidogrel (one), dual antiplatelet treatment (one), and vitamin K antagonists (one). Observational studies tested ASA (three), vitamin K antagonists (three), and clopidogrel (two). No clear evidence of efficacy was found for the overall population of individuals with migraine. Limited evidence from old RCTs-not specifically addressing the role of antithrombotic drugs for migraine prevention-and observational studies showed a potential improvement of migraine with the use of antiplatelet agents, mostly ASA, in special populations, including males, individuals with migraine with aura, and those with patent foramen ovale.

Conclusions: Evidence supporting the effectiveness of antithrombotic drugs as a preventive treatment for patients with migraine is insufficient. As preliminary data show potential improvements in special populations in whom those agents act indirectly by ameliorating vascular function, RCTs are worth conducting.

Keywords: antithrombotic; aura; microembolism; migraine; preventive treatment; prothrombotic state.

FIGURE 1

The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 flowchart of study selection. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Risk of bias analysis of randomized controlled trials included in the present systematic review. The analysis was performed according to the Cochrane Risk of Bias 2 (RoB‐2) tool. [Colour figure can be viewed at wileyonlinelibrary.com]

FIGURE 3

Risk of bias analysis of observational studies included in the present systematic review. The analysis was performed according to the Cochrane Risk Of Bias In Non‐randomized Studies of Interventions (ROBINS‐I) tool [Colour figure can be viewed at wileyonlinelibrary.com].

FIGURE 4

Promising areas for further research on antithrombotic applications in migraine. ASA, acetylsalicylic acid; CLP, clopidogrel; PFO, patent foramen ovale; RCT, randomized controlled trial; WMH, white matter hyperintensities (Created with BioRender.com). [Colour figure can be viewed at wileyonlinelibrary.com]