CGRP Antagonist Therapy for Migraine Associated with Pulmonary Arterial Hypertension in Case Series
Background
Migraine is a debilitating neurological disorder significantly impacting quality of life. Calcitonin gene-related peptide (CGRP)-targeted therapies, including monoclonal antibodies and gepants, have revolutionized migraine prevention and acute treatment. However, CGRP is also a potent endogenous pulmonary vasodilator, and its blockade is known to worsen pulmonary hypertension in experimental models. Despite widespread use, the cardiopulmonary risks of CGRP pathway inhibition in humans have not been systematically investigated, leaving a critical knowledge gap regarding potential adverse effects.
Study Design
This report details a case series of 3 patients who developed hemodynamically confirmed pulmonary arterial hypertension (PAH) while receiving CGRP-targeted therapy for migraine. The study focused on clinical presentation, diagnostic findings, and outcomes following intervention. Two patients lacked traditional PAH risk factors, while the third had suspected portal hypertension. Diagnosis of PAH was confirmed hemodynamically, and patient progress was monitored after CGRP-targeted therapy was discontinued and specific PAH treatment initiated.
Results
All 3 patients presented with markedly elevated pulmonary vascular resistance, a hallmark of pulmonary arterial hypertension, while undergoing CGRP-targeted therapy. This observation highlights a potential adverse effect of these widely used migraine treatments. Importantly, 2 patients demonstrated clinical improvement after the CGRP-targeted therapy was discontinued and standard PAH treatment protocols were initiated. This temporal association suggests a plausible link between CGRP pathway inhibition and the development or exacerbation of PAH. The abstract does not provide specific numerical values for pulmonary vascular resistance or other hemodynamic parameters, but emphasizes the 'markedly elevated' nature. > The most compelling finding is that 2 out of 3 patients experienced clinical improvement upon cessation of CGRP-targeted therapy and initiation of PAH treatment, suggesting a direct impact.
Key Findings
- Three patients developed hemodynamically confirmed pulmonary arterial hypertension (PAH) while on CGRP-targeted migraine therapy.
- Two of the three patients lacked traditional PAH risk factors, suggesting a direct link to CGRP therapy.
- All patients exhibited markedly elevated pulmonary vascular resistance upon PAH diagnosis.
- Two patients improved clinically after discontinuing CGRP-targeted therapy and initiating PAH treatment.
Why It Matters
This case series raises a crucial safety signal for clinicians prescribing CGRP-targeted therapies for migraine. Vigilance for cardiopulmonary symptoms is now warranted in patients receiving these treatments, particularly given CGRP's known role in pulmonary vasodilation. While causality cannot be definitively established from these cases, the biological plausibility and temporal association suggest a need for further systematic study, potentially impacting future prescribing guidelines and patient monitoring protocols. This finding could influence the risk-benefit assessment for patients with pre-existing cardiovascular or pulmonary conditions, or those who develop new symptoms while on therapy, potentially leading to changes in how these peptides are combined or timed with other medications.
cgrp-antagonist
migraine
pulmonary-hypertension
case-series
safety-signal
cardiopulmonary