Vascular Safety of Aimovig (erenumab) For Migraine Prevention. 2023
Vascular Safety of Aimovig (erenumab) For Migraine Prevention.
Aimovig (erenumab) is one of the 3 new CGRP drugs for migraine prevention first introduced by the FDA in America in May of 2018. CGRP stands for calcitonin gene-related protein and is one of the 3 inflammatory neurochemicals that come out during the migraine process.
CGRP causes inflammation and vasodilation of cerebral arteries and inflammation of the thalamus which is the brain’s pain center.
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The Migraine Timing Cycle
Chronic migraine is defined as 15 or more headaches per month, 8 of which have migraine features. Episodic migraine is defined as 14 or less headaches per month.
It is known that these neurochemicals are released by the migraine process by experimental research wherein a patient was given a drug to start the migraine and blood was collected from their jugular vein by a needle in their neck as the neurochemicals were on their way from the brain, to the liver to be metabolized, and then to leave the body in the toilet.
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The original research studies with Aimovig (erenumab) found no significant cardiovascular side effects studying a normal population of migraine patients, but the question of whether Aimovig (erenumab) would be free of significant side effects studying a group of patients with known cardiovascular disease hadn’t been reported.
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This is an article by Britt Talley Daniel MD, retired member of the American Academy of Neurology, the American Headache Society, migraine textbook author, podcaster, and blogger.
Aimovig is a new migraine prevention drug self given by the patient subcutaneously once a month. Aimovig has few side effects, can be used with all drugs, and produces significant prevention of migraine attacks. It has no untoward effect on patients with coronary artery disease, previous heart attack or angina, or stroke risk.
Related questions.
What are the drug interactions with Aimovig (erenumab)? Aimovig (erenumab) has no drug interactions and can be taken with any other drug. It is made by DNA polymerization and then injected in the body.
What are the side effects from taking Aimovig (erenumab)? Serious side effects are hypersensitivity reaction; common side effects are injection site reaction, constipation, and muscle cramps or spasms.
Serious side effects are very rare and the common side effects are not bad. Constipation may occur in 3% but it improves with time. The injection site reaction is like the small bruise one gets following getting blood drawn in the patient’s arm for lab studies.
Small bruise from subcutaneous injection
Is migraine associated with an increased risk of vascular events? Yes, migraine is comorbid or associated with many cardiovascular diseases.
Stroke, particularly ischemic cerebral infarction, which is increased with migraine with aura by 6%.
Hypertension is one of the most common risk factors for development of atherosclerotic (hardening and narrowing of the arteries). Hypertension has a 10 % link to migraine.
Angina/myocardial infarction. Angina is organic heart disease with symptoms of chest related or arm, chin, back, or neck referred pain that comes with exertion or anxiety. Angina relates to heart disease. Myocardial infarction is a medical term for a heart attack and signifies tissue damage to the heart muscle.
The precise biological mechanism by which migraine with and without aura may increase the risk of angina and myocardial infarct is currently unknown but statistically relevant.
Raynaud’s Disease and Raynaud’s Phenomenon are associated with migraine. Raynaud’s phenomenon and Disease are neurovascular symptoms relating to constriction and dilatation of small arteries.
Congenital Heart Disease. A recent study found an increase in the prevalence of migraine among adults with congenital heart disease. The frequency of migraine was highest among congenital heart disease subjects with right-to-left shunt (52%) followed by those with left-to-right shunt (44%).
Mitral Valve Prolapse This is a common heart condition found in 1.5 to 2% of the population, and in most persons does not cause symptoms. It results from descent of part of the mitral valve, on the left side of the heart, between the small chamber (atrium) and the large chamber that pumps blood to the body (ventricle).
Mitral valve prolapse symptoms are chest pain, rapid heartbeat, and anxiety. The relationship between migraine and mitral valve prolapse is uncertain, yet the association has been reported.
Patent foramen ovale (PFO) is found in as many as 25% of persons early in life, and usually spontaneously closes on its own. Yet, patent foramen ovale may extend into adulthood and be associated with migraine.
In many individuals (as many as 25% or more), the foramen ovale may persist unclosed (patent) into adulthood. A number of studies have suggested that individuals with migraine are more likely to have a patent foreman ovale (PFO), and this association is most evident in those whose attacks of migraine may be accompanied by aura.
The means by which a patent foramen ovale may relate to migraine is not understood, yet there is a statistical relationship between the two. Most of the literature has clustered around PFO and migraine with aura.
Atrial septal defect (ASD) is statistically related to migraine, yet like PFO, surgery to close the defect is not medically indicated.
What are the benefits of Aimovig (erenumab)? What are the benefits from using Aimovig (erenumab)? Half of patients get 50 % reduction in migraine headaches. Another 25 % of patients get 75 % reduction in migraine and another 25 % of patients, the so-called “super responders” get 100 % reduction of migraine headaches.
These are astounding results for migraine therapy and much better than the results of any previously used migraine preventive drug.
Kudrow, et al, wrote in Neurology 2020;94:e497-510 on “Vascular safety of Aimovig (erenumab)for migraine prevention.
This was a vascular safety report on Aimovig (erenumab)?
The doctors collected data from 4 clinical trials lasting 12 weeks. They studied 2,443 patients with a year history of episodic or chronic migraine in North America, Europe, Turkey, and Russia.
These trials excluded patients with vascular events in the previous 12 months.
An independent committee analyzed patient adverse events.
How were the study patients treated? Half of the patients were given placebo treatment and the other half were given standard Aimovig (erenumab) treatment which was monthly subcutaneous injections of either 70 or 140 mg.
What were the results of the Kudrow study? The 3 groups had similar rates of adverse events in general and vascular adverse events specifically.
The result in Neurology was: “This study examined the vascular safety of Aimovig (erenumab) in migraine prevention trials; Aimovig (erenumab) does not increase the risk of vascular adverse events.”
“The results of this [safety] study provide some evidence that CGRP receptor inhibition did not aggravate myocardial ischemia in at-risk population of patients with stable angina compared to placebo and contribute to the growing body of evidence supporting the safety profile of Aimovig,” said Amaal J. Starling, MD, at Mayo Clinic AZ, and co-author of the study.
Depre, et al, wrote in Headache. 2018 May; 58(5): 715–723. On “A Randomized, Double‐Blind, Placebo‐Controlled Study to Evaluate the Effect of Erenumab on Exercise Time During a Treadmill Test in Patients With Stable Angina.”
What was the purpose of Depre’ work? To determine the potential impact of erenumab, a human anti‐calcitonin gene‐related peptide (CGRP) receptor monoclonal antibody, on total exercise time (TET), time to exercise‐induced angina, and ST depression in a double‐blind, placebo‐controlled study in patients with stable angina due to documented coronary artery disease.
Depre noted that “The relative importance of the CGRP receptor pathway during myocardial ischemia has not been established.”
Depre’s methods were: An exercise treadmill test was conducted following a single IV infusion of erenumab 140 mg or placebo. The primary endpoint was the change from baseline in exercise duration as measured by TET with a noninferiority margin of −90 seconds. Safety follow‐up visits occurred through week 12. Eighty‐eight participants were included in the analysis.
The results were: He presented a 12-week, randomized, double-blind study in which 89 patients with stable angina were assigned to a single IV infusion of 140 mg of erenumab or placebo followed by an exercise treadmill test.
Reassuringly, the CGRP inhibitor had no adverse effect on exercise time, time to onset of at least 1 mm of ST segment depression. Nor did it affect heart rate or blood pressure during or after exercise.
Depre’s conclusions were: Aimovig (erenumab) did not adversely affect exercise time in a high cardiovascular risk population of patients, supporting that inhibition of the canonical CGRP receptor does not worsen myocardial ischemia.
Depre’ explained: “Although no signal of any cardiovascular issues arose in four randomized, double-blind clinical trials or in the long-term extension studies, it was appropriate to take a more focused look at erenumab’s effects in a high-risk population with stable angina and proven ischemic coronary artery disease.
That’s because CGRP is a neuropeptide that not only affects migraine, it also acts as a cytoprotective mediator released by cardiac nerve fibers during myocardial ischemia. Thus, erenumab posed a theoretic cardiovascular risk.”
Bottom line. Aimovig (erenumab) is safe to use for migraine patients with vascular risk factors.
Safe to use
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Britt Talley Daniel MD