Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk and in Pregnant Women

Study Overview
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Brief Summary
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Researchers are evaluating the safety of triptan treatment of migraine in individuals with elevated cardiovascular risk and in pregnant women.

Detailed Description
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Migraine is a very common condition that can be associated with significant morbidity. For the acute treatment of migraine attacks, the use of triptans, NSAIDs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments are associated with improved pain and function. The effectiveness of these therapies has been documented in various studies and summarized in systematic reviews. However, systematic reviews have demonstrated evidence gaps in two groups of patients that were excluded from treatment trials. These are patients with cardiovascular disease or at high risk of cardiovascular events, and pregnant women. Triptans, the mainstay treatment for migraine attacks and the one supported by the highest quality evidence, are considered vasoactive and are contraindicated per formulary in individuals who have a history of myocardial infarction, stroke, or uncontrolled vascular risk factors such as hypertension. These individuals are usually excluded from randomized trials. Similarly, pregnant women have been excluded from triptans trials and the observational studies offered low certainty evidence about their safety. Yet, 44% of surveyed members of the American Headache Society reported being somewhat or very comfortable using triptans in pregnancy. Therefore, the investigators intend to evaluate the safety of triptan treatment of migraine in individuals with cardiovascular disease or multiple cardiovascular risk factors, and in pregnant women in two target trial emulations.

Official Title
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Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk and in Pregnant Women

Conditions
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Migraine, Cardiovascular Diseases, Pregnancy

Intervention / Treatment
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* Drug: Acute migraine treatment with any prescribed triptans
* Drug: Standard of care management of acute migraine without triptans


Participation Criteria
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Eligibility Criteria
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Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: Inclusion: Aged >=18 years At least 1 year history of migraine with or without aura Confirmed cardiovascular or cerebrovascular disease, including myocardial infarction (MI), coronary artery disease (CAD), cerebrovascular disease, stroke; or at least 2 cardiovascular risk factors, including diabetes, hyperlipidemia, hypertension, obstructive sleep apnea, peripheral vascular disease; At least 1 year of prior triptan treatment or no previous triptan treatment. Exclusion: • Prescription of ergot alkaloids or dihydroergotamine within 60 days before or after starting treatment Treatments of Migraine With Triptans in Pregnant Women Inclusion: Aged >=18 years Pregnant woman Diagnosis of episodic or chronic migraine with or without aura before pregnancy Exclusion: • Prescription of ergot alkaloids or dihydroergotamine <= 60 days before pregnancy or during pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cardiovascular Risk Group Treated with Triptans<br>Subjects with diagnosis of migraine and cardiovascular disease, cerebrovascular disease and/or two or more cardiovascular risk factors who received Triptans as part of clinical care. | Drug: Acute migraine treatment with any prescribed triptans<br>* Sumatriptan, treximet (sumatriptan/naproxen combination), zolmitriptan, naratriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. No restriction on dose, frequency, duration, or delivery routes.<br>* Other names: Triptans;|
| Cardiovascular Risk Control Group Treated with No Triptans<br>Subjects with who did not received Triptans as part of clinical care. | Drug: Standard of care management of acute migraine without triptans<br>* Any standard of care management without triptans<br>* Other names: No triptans;|
| Pregnant Women Group Treated with Triptans<br>Subjects diagnosed with migraine that received Triptans as part of clinical care during pregnancy. | Drug: Acute migraine treatment with any prescribed triptans<br>* Sumatriptan, treximet (sumatriptan/naproxen combination), zolmitriptan, naratriptan, rizatriptan, almotriptan, eletriptan, and frovatriptan. No restriction on dose, frequency, duration, or delivery routes.<br>* Other names: Triptans;|
| Pregnant Women Control Group Treated with No Triptans<br>Subjects that did not receive Triptans as part of clinical care during pregnancy. | Drug: Standard of care management of acute migraine without triptans<br>* Any standard of care management without triptans<br>* Other names: No triptans;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiovascular events (MACE) | Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: number of subjects to experience major adverse cardiovascular events (MACE) which consists of all-cause death, nonfatal myocardial infarction, nonfatal stroke, heart failure, transient cerebral ischemia, or revascularization | 60 days of starting treatment | 
| Full term birth | Treatments of Migraine With Triptans in Pregnant Women: number of pregnant women to have a full term birth | 39 0/7 weeks of gestation through 40 6/7 weeks of gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| all-cause death | Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: all-cause death | 60 days of starting treatment | 
| Nonfatal myocardial infarction | Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: nonfatal myocardial infarction | 60 days of starting treatment | 
| Nonfatal stroke | Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: nonfatal stroke | 60 days of starting treatment | 
| Heart failure | Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: Heart failure | 60 days of starting treatment | 
| Transient cerebral ischemia | Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: transient cerebral ischemia | 60 days of starting treatment | 
| Revascularization | Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk: revascularization | 60 days of starting treatment | 
| Pre-term delivery | Treatments of Migraine With Triptans in Pregnant Women: Pre-term delivery | 37 0/7 weeks of gestation through 38 6/7 weeks of gestation | 
| Cesarean section delivery | Treatments of Migraine With Triptans in Pregnant Women: cesarean section delivery | up to delivery | 
| Spontaneous abortions/miscarriage | Treatments of Migraine With Triptans in Pregnant Women: Spontaneous abortions/miscarriage | up to delivery | 
| Fetal death/stillbirth | Treatments of Migraine With Triptans in Pregnant Women: Fetal death/stillbirth | up to delivery | 
| Intra-uterine growth restriction | Treatments of Migraine With Triptans in Pregnant Women: Intra-uterine growth restriction | up to delivery | 
| Eclampsia/preeclampsia | Treatments of Migraine With Triptans in Pregnant Women: Eclampsia/preeclampsia | up to delivery | 
| Tubal or ectopic pregnancy | Treatments of Migraine With Triptans in Pregnant Women: Tubal or ectopic pregnancy | up to delivery | 
| Major fetal malformations | Treatments of Migraine With Triptans in Pregnant Women: Major fetal malformations | up to delivery |