Getting to the Heart of the Matter: Migraine, Triptans, DHE, Ditans, CGRP Antibodies, First/Second‐Generation Gepants, and Cardiovascular Risk

Abstract

Premise The science of migraine pathophysiology has advanced significantly since the 1930’s. Imaging techniques, neurochemical analysis, clinical trials, and the clinical experience of providers treating migraine patients have not only sharpened our understanding of the disease, but have also led to the development of novel neural‐based targets. Targeted therapies such as calcitonin gene‐related peptide (CGRP) antibodies and “Second Generation” CGRP receptor antagonists (Gepants) have not only demonstrated efficacy, but have not resulted in any significant cardiovascular nor other serious adverse events. “First Generation” Gepants were associated with liver toxicity. Problem Triptans and dihydroergotamine (DHE) are contraindicated in patients with hemiplegic and basilar migraine based on theories of migraine pathophysiology from the 1930s. While our understanding of migraine has evolved substantially, perceived concerns of safety from almost a century ago continue to preclude their use in certain patient populations. Potential solution While migraine aura was once thought to be primarily due to vasoconstriction, current evidence debunks this concept. For instance, hemiplegic migraine is the consequence of genetic mutations resulting in channelopathies without evidence of cerebral ischemia or infarction. Evidence of basilar artery constriction as postulated in basilar migraine is also lacking. This recognition has led the International Headache Society to rename basilar‐type migraine to migraine with brainstem aura. The following discussion reviews current literature with respect to migraine as a neuronal disorder, as well as the published data on the safety of triptans, DHE, Ditans (a novel class of 5‐HT1f receptor agonists), CGRP antibodies, and Gepants.

Dihydroergotamine (DHE) – Then and Now: A Narrative Review

“…The PK data confirmed the high C max seen with IV administration (58,321 pg/mL) compared to the C max with MAP0004 (2475 pg/mL after first dose and 3063 pg/mL after second dose) that was effective in the clinical studies. 27,76 A recent review examined the evidence of cardiovascular safety concerns with DHE (and triptans) and suggested that evidence for harm with these 5HT agonists is missing 81 even for those suffering from what is now classified as Migraine with Brainstem Aura (MBA) or Hemiplegic Migraine. 82 The final concluding statement from the review reminded us of the primary role of neuronal processes in the pathophysiology of migraine, rather than vascular.…”

An Explainable Multimodal Neural Network Architecture for Predicting Epilepsy Comorbidities Based on Administrative Claims Data

“…According to SHAP analysis, the most relevant features in the DeepLORI model for migraine relate to the prior existence of headaches and the use of drugs for the nervous system, which are typically used to treat headaches. In addition, many drugs used for treating headaches are known to affect the liver (Mathew and Klein, 2019;Valade, 2019). It is known that females are more affected by migraine than males, and that migraine is age-dependent (Victor et al, 2010).…”

The potential of lasmiditan in migraine

“…Diseases such as hemiplegic migraine or migraine with complicated aura also do not allow the intake of a triptan. 5 Among the risk factors for cardiovascular disease, obesity is on the rise, also affecting a younger population. 6 Together with other risk factors; for example, hypercholesterinemia or diabetes, these changes in the general population may also lead to significantly more migraine patients with cardiovascular disease, who are in need for acute antimigraine drugs without vasoactive properties.…”

“…Diseases such as hemiplegic migraine or migraine with complicated aura also do not allow the intake of a triptan. 5…”