In a small real-world cohort of migraine 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.'
Key Findings
Results
CGRP pathway inhibitors were not associated with recurrent cerebrovascular events or worsening of underlying cardiac disease in patients with prior ischaemic events.
No recurrent cerebrovascular events were observed during treatment follow-up.
No worsening of underlying cardiac disease was observed during treatment.
Serial neuroimaging, available in a subset of patients, showed no new ischaemic lesions.
Total follow-up amounted to 31 patient-years of exposure, with follow-up up to 5 years.
Authors characterized these safety findings as 'reassuring but only exploratory and hypothesis-generating requiring further confirmation.'
Methods
Among 420 consecutive migraine patients treated with CGRP pathway inhibitors, 17 (4%) had a history of cerebrovascular and/or cardiovascular disease and met inclusion criteria.
Eligible patients had a history of ischaemic stroke, transient cerebral ischaemic attack, or ischaemic heart disease.
Median age of the included cohort was 54.5 years, 76% were female.
82% of included patients had chronic migraine.
Median time from prior vascular event to treatment initiation was 5.0 years (IQR 4.5).
Such patients were noted to have been 'largely excluded from clinical trials' of CGRP pathway inhibitors.
Results
The majority of patients with prior cerebrovascular or cardiovascular disease achieved clinically meaningful migraine reduction with CGRP pathway inhibitors.
13 of 17 patients (76%) achieved ≥50% reduction in monthly migraine days.
Treatment response in chronic migraine subgroup was 10 out of 14 patients.
Treatment response in episodic migraine subgroup was 3 out of 3 patients.
This response rate was observed in a cohort that was 82% chronic migraine.
Background
This study addressed a specific evidence gap, as patients with prior ischaemic events were largely excluded from clinical trials of CGRP pathway inhibitors.
The study used a prospective real-world registry from a tertiary Headache Centre.
The registry included 420 consecutive migraine patients treated with CGRP pathway inhibitors.
The analysis was conducted to assess clinical characteristics, treatment response, and vascular outcomes during follow-up.
The study population included patients with history of ischaemic stroke, transient cerebral ischaemic attack, or ischaemic heart disease.
Conclusions
The authors explicitly characterized the findings as exploratory and hypothesis-generating rather than confirmatory.
The cohort size was small (n=17) with 31 total patient-years of exposure.
Serial neuroimaging was only available in a subset of patients, not the full cohort.
The authors stated the findings 'require further confirmation.'
The study design was a real-world registry analysis, not a randomized controlled trial.
What This Means
This research suggests that a class of migraine-prevention drugs called CGRP pathway inhibitors may be safe for people who have previously had a stroke, mini-stroke (TIA), or ischemic heart disease. These drugs work by blocking a protein involved in triggering migraines and are among the most effective migraine preventives available. However, because people with prior vascular events were left out of the original clinical trials, doctors have had very little guidance on whether it is safe to prescribe them to this group of patients.
Researchers at a Swiss headache center tracked 17 such patients who were given CGRP pathway inhibitors, following them for a combined total of 31 patient-years — with some individuals followed for up to 5 years. During this entire period, no patient had a recurrent stroke, mini-stroke, or worsening heart condition, and brain scans in a subset of patients showed no new areas of damage. Additionally, 76% of patients achieved at least a 50% reduction in the number of days per month they experienced migraines, suggesting the drugs were also effective in this population.
This research suggests that CGRP pathway inhibitors may be a viable and effective migraine treatment option even for people with a history of vascular disease. However, the authors themselves stress that the study is small and should be considered preliminary and exploratory. Larger studies are needed to confirm these findings before firm clinical conclusions can be drawn.
Bellotti A, Noseda R, Masciullo R, Staedler C, Gobbi C, Zecca C. (2026). Long-term safety of CGRP pathway inhibitors in migraine patients with prior cerebrovascular or cardiovascular disease.. Journal of neurology. https://doi.org/10.1007/s00415-026-14099-z