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An initial triptan prescription was linked with ischemic stroke and myocardial infarction for people with a high-risk cardiovascular profile, a case-crossover study in Denmark found.

Among more than 400,000 people who redeemed their first triptan prescription, triptan exposure raised the odds of an ischemic event, but the risk for most users was very low, according to Jesper Hallas, MD, DMSc, of Odense University Hospital in Denmark, and colleagues.

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 .

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.

Triptans (sumatriptan, rizatriptan, and others) are used to treat acute migraine; they selectively bind to serotonin receptors 5-HT1B and 5-HT1D. Prescribing information lists a history of cardiovascular disease as a and advises caution when prescribing triptans to patients with vascular risk factors.

Some observational studies show either no association or a low risk of cardiovascular outcomes with triptan use, Hallas noted in a . "We interpreted this scenario as a matter of confounding: that the patients who received triptans would have a lower cardiovascular [risk] profile than those who did not receive triptans," he said. "If you cannot adjust for that completely, it will look as if triptans are either innocuous, or it might even look as if they are beneficial, in terms of having ischemic events."

To counter this, Hallas and colleagues used a case-crossover design in which the past experience of each case patient served as his or her own control. This helped ensure that confounders like genetic disposition, atherosclerosis, smoking behavior, or being overweight cancelled out. The researchers calculated odds ratios for relationships between first-ever triptan prescription and ischemic outcomes, comparing triptan exposure in the 2-week period up to the event with four 2-week reference periods.

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 also was higher in patients who had hypertension or who were younger than 60 years.

The absolute risk of ischemic events was low in this study, "something on the order of 1 in 30,000 initiators of triptans on the average," Hallas pointed out. "If you have a high-risk profile, the risk is more than 1 in 30,000," he said. "If you have a low-risk profile, it's less than 1 in 30,000, and it's probably close to nothing."

Timing also is an important variable, noted stroke and headache specialist Hans Christoph Diener, MD, PhD, of the University Duisburg-Essen in Germany, who wasn't involved with the study.

The association between triptans and ischemic events "would be valid only if the vascular events happened within the time frame of the half-life of the drug (48 hours)," Diener said in an email to MedPage Today. "Otherwise, this is due to undetected confounders."

The analysis had several limitations, the researchers acknowledged. Exposure was based on prescription redemption, and when or whether patients ingested a triptan medication was unknown. Only a few people had ischemic events in the study, "warranting careful interpretation of our findings, particularly for the subanalyses," they added.

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