Neurological

Migraine Management: How To Treat Patients With Vascular Disease

The incidence of vascular disease, including arterial hypertension, coronary artery disease, and stroke, has been linked to migraines. The presence of these vascular diseases in migraineurs can affect treatment options. Treatments that target the severity and frequency of migraines and also improve vascular comorbidity are considered.

A review published in Headache discusses the possible treatment options for acute migraine attacks and for migraine prevention in patients with vascular disease and discusses the relationship between treatment with triptans and the risk of vascular disease. 1

Triptans are the most commonly prescribed treatments for acute migraine attacks; however, these drugs are contraindicated in patients with uncontrolled arterial hypertension, coronary artery disease (CAD), and who have had a stroke or transient ischemic attack. 1

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The relationship between migraines and arterial hypertension

Several studies have looked at the relationship between migraines and high blood pressure, with data suggesting a positive association between the two entities; High blood pressure can make migraine attacks more frequent and more severe. 2.3

Several antihypertensive drugs may be useful in migraine prophylaxis, particularly beta blockers, angiotensin converting enzyme inhibitors, and angiotensin II receptor blockers.1,2

While acetylsalicylic acid, paracetamol and NSAIDs can be used to treat migraines in patients with arterial hypertension, triptans should not be used in patients with uncontrolled hypertension, although the definition of “uncontrolled” in the literature has been vague.1

A meta-analysis to determine the effectiveness of preventive pharmacological treatments for migraine in adults found that various beta blockers, including propranolol, metoporlol, atenolol and nadolol, as well as the angiotensin converting enzyme (ACE) inhibitors captopril and lisinopril and angiotensin receptor blockers (ARB) Candesartan, were superior to placebo in reducing the monthly frequency of migraines by 50% or more. 4

In a review of randomized trials, Tullo and colleagues examined the effectiveness of triptans in treating acute migraines in patients with a history of arterial hypertension. There were no increases in blood pressure or heart rate in patients with hypertension during treatment with triptans, and tolerability was similar in patients with and without hypertension. However, patients with hypertension tended to be less responsive to triptans than patients with normotension

Given the available data and in accordance with FDA approval, triptans should not be used for acute migraine attacks in patients with uncontrolled high blood pressure, especially during a hypertensive crisis. In terms of migraine prophylaxis, beta-blockers and angiotensin-inhibiting drugs can be considered to prevent migraine attacks and control blood pressure. 1.4

Migraines with and without aura and risk of cardiovascular disease (CVD)

The risk of cardiovascular disease and myocardial infarction (MI) is increased in patients with migraines with or without aura and regardless of drug therapy. 1

A meta-analysis of 16 observational cohort studies of more than 1.1 million people found that migraines were associated with a higher risk of serious adverse cardiovascular and cerebrovascular events, mainly secondary to a higher risk of long-term stroke and MI. Compared to patients without aura, patients with aura had poorer cardiovascular and cerebrovascular outcomes, including stroke and MI.6

Triptans are contraindicated in patients with ischemic heart disease because of concerns about coronary vasospasm, which could lead to myocardial ischemia. However, it is now believed that these drugs activate the 1D receptors of serotonin (5-HT)

According to the FDA approval document for sumatriptan, the contraindications to use are ischemic heart disease, ischemic CHD (angina, history of myocardial infarction, or documented silent ischemia), or coronary artery vasospasm, including Prinzemetal’s angina. However, the data published after the approval of triptans showed that the risk of acute coronary syndrome was extremely low when treating acute migraines

In patients with known angina or MI, acetylsalicylic acid can be used for acute migraines. Additional treatment options for these patients may include novel anti-migraine drugs that do not have vasoconstriction of the cerebral, coronary, and peripheral arteries, including calcitonin gene-related peptide (CGRP) antagonists and 5-HT1F agonists. However, there are no specific studies to determine the safety of these drugs in patients with active CHD. 1

While NSAIDs can be effective in acute migraines, treatment with vs. without these drugs is associated with an increased cardiovascular risk. Analysis of data by drug showed that the NSAIDs rofecoxib (relative risk 1.39; 95% CI 1.31-1.47) followed by diclofenac (relative risk 1.34; 95% CI 1.26-1 , 42) and etoricoxib (relative risk 1.27; 95% CI 1.12-1.43 were associated with the highest cardiovascular risk. 7

In the absence of contraindications, beta blockers may be the most appropriate treatment for migraine prophylaxis in patients with CHD, as these drugs are considered part of standard care after acute coronary syndrome. Other treatment options for migraine prophylaxis may include topiramate, valproic acid, and onabotulinium toxin A. Researchers believe that because of the important role of CGRP-mediated collateral vessel dilation in patients with coronary artery disease, antibodies to the molecule or its receptor should not be used as a treatment in these patients

Migraine treatment and risk of stroke

A 2-fold increased risk of stroke was found in migraineurs, especially in patients with migraines with aura.1 Mahmoud and colleagues reported that migraines were associated with a 41% increased risk of stroke (adjusted hazard ratio 1.41; 95% CI 1.25 .). -1.61), but this increased risk was limited to patients with migraines with aura (adjusted hazard ratio 1.56; 95% CI 1.30-1.87), but not in patients without aura. 6 Neurophysiological studies have one Migraine aura associated with cortical spread depression, which can predispose the brain to cerebral hypoperfusion and arterial ischemia. 8

The risk of stroke is further increased if estrogen-containing contraceptives or cigarette smoking are added

Because triptans are contraindicated in patients with cerebrovascular syndrome, including stroke and transient ischemic attack, treatment for migraine attacks in these cases may include acetylsalicylic acid, NSAIDs, lasmiditan, or CGRP antagonists. 1

Since vasoconstriction does not play a prominent role in most cases of ischemic stroke (only a quarter is caused by large vessel disease) and triptans are associated with narrowing of the extracranial but not the intracranial arteries, the researchers believe the application of triptans is contraindicated in these cases patient is not yet justified. 1

However, subarachnoid hemorrhage-induced vasospasm and reversible cerebral vasoconstriction syndrome are two forms of cerebral ischemia in which vasoconstrictive mechanisms play a crucial role, and in these patients triptans are clearly contraindicated

Beta blockers can be used to prevent migraines in people who have had a stroke or have had a history of transient ischemic attack. Onabotulinium toxin A and higher doses of acetylsalicylic acid (300 or 325 mg) can also be effective in migraine prophylaxis.

Because of the potentially limited dilation of the collateral vessels, which can be very important in connection with cerebral ischemia, the researchers believe that CGRP antagonists should not be used in patients at high risk for cerebral ischemia or recurrent cerebral ischemia. 1

The future of migraine management

The Headache Review suggests that the use of triptans in migraineurs with a history of ischemic stroke or CHD may not be absolutely contraindicated because vasoconstrictive mechanisms play no role in the pathophysiology of many vascular diseases. However, given the potential impact on the collateral vessel and decreased blood flow during the migraine aura, triptans should not be given during existing aura symptoms. Since CGRP and lasmiditan do not have vasoconstrictive properties, these drugs can be used in patients with contraindications to triptans.

References

1st servant HC. The risks or lack of migraine treatment for vascular disease. Headache. 2020; 60 (3): 649-653. doi: 10.1111 / head.13749

2. Wang YF, Wang SJ. High blood pressure and migraines: time to re-examine the evidence. Curr Pain Headache Rep. July 16, 2021; 25 (9): 58. doi: 10.1007 / s11916-021-00976-x

3. Arca KN, Halker Singh RB. The hypertensive headache: a review. Curr Pain Headache Rep. 2019; 23 (5): 30. doi: 10.1007 / s11916-019-0767-z

4. Shamliyan TA, Choi JY, Ramakrishnan R. Preventive pharmacological treatments for episodic migraines in adults. J. Gen. Intern Med. 2013; 28 (9): 1225-37. doi: 10.1007 / s11606-013-2433-1

5. Tullo V., Bussone G., Omboni S. et al. Efficacy of frovatriptan and other triptans in the treatment of acute migraines in hypertensive and normotensive patients: a review of randomized trials. Neurol Sci. 2013; 34 (Supplement 1): 87-91. doi: 10.1007 / s10072-013-1367-z

6. Mahmoud AN, Mentias A, Elgendy AY et al. Migraines and the risk of cardiovascular and cerebrovascular events: a meta-analysis of 16 cohort studies with 1,152,407 subjects. BMJ open. 2018; 8 (3): e020498. doi: 10.1136 / bmjopen-2017-020498

7. Martín Arias LH, Martín González A, Sanz Fadrique R, Vazquez ES. Cardiovascular risk from nonsteroidal anti-inflammatory drugs and classic and selective cyclooxygenase-2 inhibitors: a meta-analysis of observational studies. J. Clin. Pharmacol. 2019; 59 (1): 55-73. doi: 10.1002 / jcph.1302

8. Pietrobon D, Moskowitz MA. Pathophysiology of migraines. Annu Rev Physiol. 2013; 75: 365-391. doi: 10.1146 / ansurev-physiol-030212-183717

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