Denmark Study on Triptans

A recent case-crossover study including 429,612 individuals revealed that triptan initiation is associated with a higher risk of myocardial infarction and ischemic stroke. The risk of an ischemic event after triptan initiation was very low for the individual patient with low background cardiovascular (CV) risk.

The results published in JAMA Neurology suggest that avoiding triptan treatment due to concern about triptan-associated ischemic events is rational in patients with a high-risk CV profile. Triptans are selective serotonin 1B/1D/1F agonists that are among the first-line treatment options for acute migraine attacks.

The study supports the current US Food and Drug Administration (FDA) recommendation that triptans should not be prescribed to patients with a history of transient ischemic attack, coronary artery disease, or stroke. In patients with ischemic heart disease or previous myocardial infarction, triptans are contraindicated and caution is advised when prescribing these drugs to patients with vascular risk factors. However, controlled observational studies have either shown no association or lower risk, possibly owing to the channelling of triptans to individuals at low risk of cardiovascular outcomes, and there is no clarity on whether avoiding triptan treatment for these patients is meaningful.

Against the above background, Christian Lund Petersen, Department of Clinical Pharmacology, Odense University Hospital, Odense, Denmark, and colleagues aimed to establish whether an association between triptans and ischemic events could be demonstrated using a self-controlled design because this type of design is robust to the previously mentioned type of confounding.

For this purpose, the researchers identified all people in nationwide Danish registries initiating triptans and all the ischemic events they experienced. A case-crossover design was used to estimate odd ratios (OR) for associations between the first-ever use of triptan and ischemic outcomes, comparing triptan exposure in the two weeks up to the event with four 2-week reference periods.

Individuals redeeming a prescription for any triptan and experiencing at least 1 of 3 predefined ischemic outcomes were included from the population of Denmark. No one was excluded.

Main Outcomes

• Acute myocardial infarction
• Ischemic stroke
• Nonspecified stroke

Key Findings

• 429,612 individuals (median age, 38 years; 75.8% female) were identified who redeemed a first prescription for a triptan in the study period.
• Of these patients, 0.003% had a myocardial infarction with the first triptan prescription in either a focal or referent window (odds ratio [OR], 3.3).
• 0.004% had ischemic stroke (OR, 3.2).
• 0.008% had ischemic/nonspecified stroke (OR, 3.0).
• Case patients had a median age of approximately 60 years and had a high-risk cardiovascular profile.

"The results suggest that although triptans use may be associated with a short-term higher risk of stroke or myocardial infarction, this amounted to a very small number of patients initiating triptans," the research team wrote.

"Triptans are generally considered safe in patients with low cardiovascular risk, and our findings do not raise concern about triptan use in this population group," they concluded.

Reference

Petersen CL, Hougaard A, Gaist D, Hallas J. Risk of Stroke and Myocardial Infarction Among Initiators of Triptans. JAMA Neurol. Published online February 05, 2024. doi:10.1001/jamaneurol.2023.5549