Triptans and heart disease risk

Triptans should not be used in patients with previous cardiovascular risk, myocardial infarction or stroke. Triptan use with other patients is benign.

This is an article by Britt Talley Daniel MD, retired member of the American Academy of Neurology, Migraine textbook author, Podcaster, YouTube video producer, and Blogger.

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History of triptans for migraine.

Triptans came out in 1990 first in an injectable form as Imitrex 6 mg subcutaneous. This application was named generic as sumatriptan and was always considered the highest dose of any of the triptans, 100 mg in the brain, and the fastest, 10 minutes when given subcutaneously.

After Imitrex there were five other triptans introduced. A list of current triptans is:

Zomig (Zolmatriptan) should decrease the dose by 50% if taken with Tagamet (Cimetidine). Comes as a 2.5 mg or 5 mg tab to be taken one as needed for migraine, trying the 2.5 mg dose size first and moving up to 5 mg (max 10mg/day). Dose at onset 2.5 or 5 mg, may repeat in 2 hours. Also comes as a dissolvable tablet 2.5, 5 ZMT and as a nasal spray 2.5, 5 mg. Rebound potential. Limit to 2 treatment days/week.

Maxalt (Rizatriptan) comes as a MLT (melt in your mouth) 10 mg wafer and 5, 10 mg tablets. Both are absorbed in the stomach and the MLT, which some patients consider more convenient, is absorbed slower than regular Maxalt. Should reduce the dose by 50% if taken with Inderal (Propranolol). Dose is 1 at onset, may repeat in 2 hours, or take another dose 2 hours later. Maxalt is the only triptan that can be dosed 3 tablets/day. Max 30 mg/day. Rebound potential. Limit to 2 treatment days/week.

Axert (Almotriptan) Comes as a 6.25 and 12.5 mg tablet. In controlled clinical trials, single doses of 6.25 mg and 12.5 mg of Axert tablets were effective for the acute treatment of migraines in adults, with the 12.5-mg dose tending to be more effective. Dose is 1 at onset, may repeat in 2 hours. Rebound potential. Limit to 2 treatment days/week.

Relpax (Eletriptan) Comes as a 20 and 40 mg tablet. The 40 mg tablet seems to work the best. Dose is 1 at onset, may repeat at 2 hours. Contraindicated with Antifungals, Macrolide Antibiotics, and Protease Inhibitors. Rebound potential. Limit to 2 treatment days/week.

Amerge (Naratriptan)—2.5 mg tablet which is the initial dose. May repeat in 2 hours. Onset is 1-2 hours. Amerge is a specialty niche migraine medication for those whose migraine generator in the brain produces a long, slow onset profile. This drug stays around long enough to outlast this type of migraine. The duration of activity is long—6 hours as opposed to 2-3 hours for most of the other triptans, except Frova. Rebound potential. Limit to 2 treatment days/week.

Frova (frovatriptan) ---Onset 1-2 hours. Good for migraineurs with long duration headache generators. It has a very long duration (26-hour half-life) and lasts four times longer than any other triptan. Thus, it is the drug of choice for menstrual migraine. Taking birth control pills or Inderal may increase blood levels of Frova. Treat with an initial 2.5 mg dose, may repeat in 2 hours. Rebound potential. Limit to 2 treatment days/week.

     Drug                Onset             Usual dose               Maximum 24 hours       Duration of Activity

     Imitrex

     Sumatriptan   

     Oral tablet     15-30 min        50-100 mg                200 mg                            2.5 hours

     Treximet       15                        1 tablet                      2 tablets                          same

     Nasal Spray   10 min               5, 20 mg                   40 mg                              same

     Subcu            10 min               3, 4, 6 mg                  12 mg                              same

     Dose Pro       10 min               6 mg                          12 mg                              same 

     Zomig

     Zolmitriptan

     Oral tablet     30 min              2.5, 5 mg                  10 mg                                 3 hours

     Nasal Spray  10 min              2.5, 5 mg                   10 mg                                same

     Maxalt

     rizatriptan     30 min              10 mg                        30 mg                                2-3 hours

     Axert

     Almotriptan  30 min              6.25, 12.5 mg          25 mg                                4 hours

     Relpax

     Eletriptan      30 min              20, 40 mg                80 mg                                 4 hours

     Amerge

     naratriptan    1-2 hr                2.5 mg                      5 mg                                    6 hours

     Frova

     Frovatriptan  1-2 hr               2.5 mg                      5 mg                                  


Pharmacologic action of triptans

Triptans activate serotonin 5-HT1B and 5-HT1D receptors, producing cranial vasoconstriction and inhibiting pro-inflammatory neuropeptide release.

Warnings for triptans

Early clinical studies reported that triptans produced problems in persons with previous myocardial infarction, stroke, hypertension, or cardiovascular risk. The current list of FDA contraindications is:

             History of coronary artery disease or coronary artery vasospasm (4)

•           Wolff-Parkinson-White syndrome or other cardiac accessory conduction disorders.

•           History of stroke, transient ischemic attack, or hemiplegic or basilar migraine.

•           Peripheral vascular disease (4)

•           Ischemic bowel disease (4)

•           Uncontrolled hypertension (4)

•           Recent (within 24 hours) use of another 5-HT1 agonist (e.g., another

             triptan) or of an ergotamine-containing medication (4)

•           Concurrent or recent (past 2 weeks) use of monoamine oxidase-A inhibitor

•           Hypersensitivity to IMITREX (angioedema and anaphylaxis seen) (4)

•           Severe hepatic impairment (4)

Warnings and Precautions ----------------------­

•           Myocardial ischemia/infarction and Prinzmetal’s angina:

•           Arrhythmias: Discontinue IMITREX if occurs. (5.2)

•           Chest/throat/neck/jaw pain, tightness, pressure, or heaviness:

•           Cerebral hemorrhage, subarachnoid hemorrhage, and stroke:

•           Gastrointestinal ischemic reactions and peripheral vasospastic reactions:

Triptans work better and faster than new acute therapy migraine treatment drugs.

A recent study has found that newer developed acute therapy drugs for migraine do not work as well as the triptans. The new medication drugs for migraine considered for this study are the CGRP inhibitors Nurtec (rimegepant), Ubrelvy (ubrogepant), and Reyvow (lasmiditan).

Read my article, NEW MIGRAINE DRUGS DO NOT WORK AS WELL AS TRIPTANS 2024 on my website www.doctormigraine.com.

New article on triptan use and heart disease.

February 5, 2024

Risk of Stroke and Myocardial Infarction Among Initiators of Triptans

Christian Lund Petersen, Anders Hougaard, David Gaist4, Jesper Hallas, MD.

Risk of Stroke and Myocardial Infarction Among Initiators of Triptans

Using a nationwide Danish registration, the authors asked the question, “Is the use of triptans associated with ischemic events to an extent that warrants current contraindication in patients with ischemic risk factors?”

Findings  In this case-crossover study including 429 612 individuals, triptan use was associated with a higher risk of ischemic events, but the risk for the individual user was very low. Patients with ischemic outcomes generally had a profile of high cardiovascular risk.

Meaning  Results suggest that avoiding triptan treatment due to concern of triptan-associated ischemic events is rational in patients with a high-risk cardiovascular profile.

In total, 11 people (0.003%) had myocardial infarction with their first triptan prescription (OR 3.3, 95% CI 1.0-10.9), 18 people (0.004%) had ischemic stroke (OR 3.2, 95% CI 1.3-8.1), and 35 people (0.008%) had ischemic or unspecified stroke (OR 3.0, 95% CI 1.5-5.9), the researchers reported in JAMA Neurologyopens in a new tab or window.

Nearly all people with an ischemic event had cardiovascular risk factors. Their median age was about 60.

"The results of this study support the current U.S. Food and Drug Administration recommendation that triptans should not be prescribed to patients with a history of coronary artery disease, transient ischemic attack, or stroke," Hallas and co-authors wrote.

The study spanned January 1995 to August 2022 and included 429,612 people in Denmark who redeemed a first-ever triptan prescription. Median age was 38 and 75.8% were female.

In subgroup analyses, triptan use was associated with higher risk of myocardial infarction in patients with previous acute coronary syndrome, hypertension, and in patients younger than age 60. Risk for ischemic stroke was also higher in patients who had hypertension or who were younger than 60 years.

The following new CGRP acute therapy drugs for migraine patients carry no cardiovascular risk:

Ditan Reyvow (lasmiditan) is the first of a new treatment , called a Ditan, for the acute treatment of migraine with or without aura. Dose is 50 and 100 mg.

Gepants Nurtec (Rimegepant) is the first of a new kind of acute and preventive treatment for Migraine. Nurtec (Rimegepant) is given as a fast acting orally disintegrating 75 mg tablet to patients with episodic or chronic migraine. Nurtec dose is 75 mg OTC which means oral dissolving tablet.

Ubrelvy (Ubrogepant) is a calcitonin gene-related peptide, CGRP, receptor antagonist for the acute treatment of migraine with or without aura in adults. Dose is 50 and 100 mg.

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Britt Talley Daniel MD