Migraine Management: How to Treat Patients With Vascular Disease

In patients with known angina pectoris or MI, acetylsalicylic acid may be used for acute migraine. Additional treatment options for these patients can include novel medications for migraine that do not exhibit 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 medications in patients with active CAD.¹

While NSAIDs may be effective for acute migraine, treatment with vs without these medications are associated with an increased cardiovascular risk. Data analysis by drug indicated that 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 suitable treatment for migraine prophylaxis in patients with CAD, as these medications are considered part of the standard care following an acute coronary syndrome. Other treatment options for migraine prophylaxis may include topiramate, valproic acid, and onabotuliniumtoxin A.  Researchers believe that because of the important role of CGRP-mediated dilation of collateral vessels in patients with coronary heart disease, antibodies against the molecule or its receptor should not be used as treatment in these patients.¹

Migraine Treatment and Risk for Stroke

Patients with migraine were found have 2 times increased risk for stroke, especially for patients who have migraine with aura.¹ Mahmoud and colleagues reported migraine was associated with a 41% increased risk for stroke (adjusted hazard ratio, 1.41; 95% CI, 1.25-1.61), but this increased risk was limited to patients who had migraine with aura (adjusted hazard ratio, 1.56; 95% CI, 1.30-1.87), but not in those without aura.⁶ Neurophysiologic studies have linked migraine aura to cortical spreading depression, which may predispose the brain to cerebral hypoperfusion and arterial ischemia.⁸

The risk for stroke is further increased when adding estrogen-containing contraceptives or cigarette smoking.¹

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

Researchers believe that because vasoconstriction does not play a prominent role in most cases of ischemic stroke (only one-quarter are caused by large vessel disease) and triptans are associated with constriction of the extracranial but not intracranial arteries, the contraindication for triptans use in these patients is not yet justified.¹

However, subarachnoid hemorrhage-related vasospasm and reversible cerebral vasoconstriction syndrome are 2 forms of cerebral ischemia in which vasoconstrictive mechanisms play a vital role, and among these patients, triptans are clearly contraindicated.¹

Beta-blockers may be used to prevent migraine attacks in patients with a history of stroke or transient ischemic attack. Onabotuliniumtoxin A and higher doses of acetylsalicylic acid (300 or 325mg) may also be effective in migraine prophylaxis.

Due to the potential restricted dilatation of collateral vessels, which may be very important in the context of cerebral ischemia, researchers believe that CGRP antagonists 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 because vasoconstrictive mechanisms do not play a role in the pathophysiology of many vascular diseases, the use of triptans may not be absolutely contraindicated in patients with migraine with a history of ischemic stroke or CAD. However, in light of the potential impact on collateral vessel, and reduction of perfusion during migraine aura, triptans should not be given during existing aura symptoms. Because CGRP and lasmiditan have no vasoconstrictive properties, these drugs may be used in patients with contraindications to triptans.

References

1. Diener H-C. The risks or lack thereof of migraine treatments in vascular disease. Headache. 2020;60(3):649-653. doi:10.1111/head.13749

2. Wang YF, Wang SJ. Hypertension and migraine: time to revisit the evidence. Curr Pain Headache Rep. Jul 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 pharmacologic treatments for episodic migraine 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 migraine of hypertensive and normotensive subjects: a review of randomized studies. Neurol Sci. 2013;34(Suppl 1):87-91. doi:10.1007/s10072-013-1367-z

6. Mahmoud AN, Mentias A, Elgendy AY, et al. Migraine and the risk of cardiovascular and cerebrovascular events: a meta-analysis of 16 cohort studies including 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 of nonsteroidal anti-inflammatory drugs and classical 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 migraine. Annu Rev Physiol. 2013;75:365-391. doi:10.1146/annurev-physiol-030212-183717

This article originally appeared on Neurology Advisor