CGRP and migraine from a cardiovascular point of view: what do we expect from blocking CGRP?

Abstract

Calcitonin gene-related peptide (CGRP) is a neuropeptide with a pivotal role in the pathophysiology of migraine. Blockade of CGRP is a new therapeutic target for patients with migraine. CGRP and its receptors are distributed not only in the central and peripheral nervous system but also in the cardiovascular system, both in blood vessels and in the heart. We reviewed the current evidence on the role of CGRP in the cardiovascular system in order to understand the possible short- and long-term effect of CGRP blockade with monoclonal antibodies in migraineurs.In physiological conditions, CGRP has important vasodilating effects and is thought to protect organs from ischemia. Despite the aforementioned cardiovascular implication, preventive treatment with CGRP antibodies has shown no relevant cardiovascular side effects. Results from long-term trials and from real life are now needed.

Efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibodies for the preventive treatment of episodic migraine – an updated systematic review and meta-analysis

“…Since CGRP has important vasodilating effects and could protect organs from ischemia, the effect of CGRP blockade on cardiovascular system may be concerned. In the short-and long-term studies about animals and humans published, neither any hypertensive effect nor any negative effects regarding the development or aggravation of cardiac failure was observed [36]. Based on the findings of this meta-analysis, mAbs against CGRP (eptinezumab, fremanezumab and galcanezumab) and CGRP receptor (erenumab) could effectively prevent episodic migraine attacks without obvious adverse effects.…”

“…It's reported that most of CGRP is released from trigeminal afferents both in meningeal tissues and at the first synapse in the spinal trigeminal nucleus [35]. And CGRP receptors are distributed in the central and peripheral nervous system, as well as in the cardiovascular system [36]. Since CGRP Fig.…”

Efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibodies for the preventive treatment of episodic migraine – An updated systematic review and meta-analysis

“…Since CGRP has important vasodilating effects and could protect organs from ischemia, the effect of CGRP blockade on cardiovascular system may be concerned. In the short-and long-term studies about animals and humans published, neither any hypertensive effect nor any negative effects regarding the development or aggravation of cardiac failure was observed [36] .Based on the findings of this meta-analysis, mAbs against CGRP (eptinezumab, fremanezumab and galcanezumab) and CGRP receptor (erenumab) could effectively prevent episodic migraine attacks without obvious adverse effects. However, the majority of results obtained from the included trials are achieved at 12 weeks or 24 weeks after treatment, and thus further trials are needed to determine the long-term safety of CGRP mAbs and the durability of their effects.…”

“…It's reported that most of CGRP is released from trigeminal afferents both in meningeal tissues and at the first synapse in the spinal trigeminal nucleus [35] . And CGRP receptors are distributed in the central and peripheral nervous system, as well as in the cardiovascular system [36] . Since CGRP and mAbs cannot easily pass the blood-brain barrier, they may act in the trigeminal ganglion to influence the production of pronociceptive substances and receptors, which are transported along the central terminals into the spinal trigeminal nucleus.…”

An Evidence-Based Review of Fremanezumab for the Treatment of Migraine

“…The safety, tolerability, and clinical efficacy of fremanezumab have been consistently validated across all placebo-controlled phase 2b/3 trials in adults with episodic and chronic migraine [76,77,[80][81][82][83][84][85]. Although currently available studies provide support for fremanezumab, further studies are needed to elucidate the relationship between the pharmacodynamic activity and its mechanism; the long-term risks, especially with regard to the cardiovascular system, of chronic use of anti-CGRP monoclonal antibodies; the specific sites of action, including whether it can bind to other human calcitonin receptors; and the effect of antidrug neutralizing antibodies on long-term efficacy [90,[129][130][131][132][133].…”