Long-term safety of CGRP pathway inhibitors in migraine patients with prior cerebrovascular or cardiovascular disease.

BACKGROUND: Calcitonin gene-related peptide (CGRP) pathway inhibitors are highly effective migraine preventives, but their long-term cerebrovascular and cardiovascular safety in patients with prior ischaemic events remains uncertain, as such individuals were largely excluded from clinical trials. METHODS: We analysed data from a prospective real-world registry of migraine patients treated with CGRP pathway inhibitors at our tertiary Headache Centre. Patients with a history of ischaemic stroke, transient cerebral ischaemic attack, or ischaemic heart disease were included. Clinical characteristics, treatment response, and vascular outcomes were assessed during follow-up. RESULTS: Among 420 consecutive migraine patients treated with CGRP pathway inhibitors in our registry, 17 (4%) had a history of cerebrovascular and/or cardiovascular disease and met the inclusion criteria. These patients (median age 54.5 years, 76% female; 82% chronic migraine) contributed a total of 31 patient-years of exposure, with follow-up up to 5 years. Median time from event to treatment initiation was 5.0 years (IQR 4.5). 13 patients (76%) achieved ≥ 50% reduction in monthly migraine days (10/14 in chronic migraine; 3/3 in episodic migraine). No recurrent cerebrovascular events or worsening of underlying cardiac disease were observed during treatment. Serial neuroimaging, available in a subset, showed no new ischaemic lesions. CONCLUSIONS: In this small real-world cohort patients with prior cerebrovascular and/or cardiovascular disease, the use of CGRP pathway inhibitors was not associated with new clinical or radiological ischaemic events over 31 patient‑years of follow‑up. These safety findings are reassuring but only exploratory and hypothesis-generating requiring further confirmation.