Why are triptans contraindicated in stroke

Five medications in the triptan class are approved and available for the treatment of migraine headache. These are sumatriptan, zolmitriptan, rizatriptan, almotriptan, and naratriptan. They have similar efficacies. More than one half of patients receiving the injectable form of sumatriptan report pain relief within 30 minutes. Jamieson reviewed the safety of triptans, especially in patients with concomitant vascular disease.

There are approximately 3.4 migraine-related strokes for every 100,000 persons annually, if all patients with migraines and stroke risk factors are included. The number drops to 1.4 if patients who do not have other stroke risk factors are excluded. Thus, a history of migraine is associated with a higher risk of stroke. Triptans work by vasoconstricting the meningeal blood vessels. It has been postulated that the higher rate of vascular events in these patients may be caused by use of these anti-migraine agents. However, the relationship may not be a causal one.

Although triptans cause vasoconstriction, they are more active at cranial vasculature than in other vascular beds. Sometimes patients report chest pain after taking trip-tans, but this complaint is rarely accompanied by electrocardiographic changes. Trip-tans can probably be safely continued, if needed, unless there is other evidence that the chest pain is ischemic. Triptans should be discontinued if the pain seems to be ischemic. Because of their mechanism of action, trip-tans should not be used in patients with uncontrolled hypertension; however, triptans may be an appropriate treatment for migraine if blood pressure is well controlled.

Pregnant women are proscribed from clinical trials of triptans and should not use trip-tans until more data become available. Studies of patients younger than 18 years show that triptans appear to be safe and effective, although they are not labeled by the U.S. Food and Drug Administration for use in children.

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Numerous studies have shown that triptans are safe, even with frequent, long-term use. Drug interactions do not seem to be a problem clinically, although numerous suggestions have been made about which drug combinations to avoid, based on knowledge of the pharmacody-namics of triptans. Because they stimulate serotonin receptors, triptans should not be used with other medications that also stimulate these receptors, such as ergotamines. Although serotonin syndrome is rare, it could occur with combined use of a triptan and a selective serotonin reuptake inhibitor. Careful consideration should precede using these agents together.

Monoamine oxidase (MAO) inhibitors can increase the level of triptans in the blood and should not be used with them. Similarly, propranolol, which affects the MAO-A system, has been shown to increase the concentration of rizatriptan. The dosage of rizatriptan should be decreased if it is used with propranolol. See the accompanying table for other limitations to the use of triptans.

February 24, 2004; 62 (4) Articles

The risks of stroke, cardiovascular disease, and death in practice

First published February 23, 2004, DOI: https://doi.org/10.1212/01.WNL.0000110312.36809.7F

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Abstract

Background: Triptans are widely used to treat migraine but have been associated with stroke, myocardial infarction (MI), and ischemic heart disease (IHD) in case reports.

Objective: To estimate the incidence of stroke, cardiovascular events, and death in a migraine cohort, stratified by triptan prescription, and investigate whether the risk of these events was increased in those treated with triptans.

Methods: Migraine patients and matched nonmigraine control subjects were identified from the General Practice Research Database. Computerized records were searched for triptan prescriptions, stroke, TIA, MI, IHD, death, arrhythmia, and confounding variables. Incidence rates were calculated and migraine groups compared with controls using a Cox model, adjusting for confounders.

Results: Of 63,575 migraine patients, 13,664 were prescribed a triptan. There was no association between triptan prescription and stroke (hazard ratio [HR] 1.13; 95% CI 0.78, 1.65), MI (HR 0.93; 95% CI 0.60, 1.43), or other outcomes studied. The larger group of migraine patients not prescribed a triptan had an increased risk of stroke (HR 1.51; 95% CI 1.26, 1.82) and IHD (HR 1.35; 95% CI 1.18, 1.54) and a decreased risk of all-cause mortality (HR 0.72; 95% CI 0.65, 0.80).

Conclusions: In general practice, triptan treatment in migraine does not increase the risk of stroke, MI, cardiovascular death, IHD, or mortality. Triptans are prescribed to those less at risk of these events.

• Received June 20, 2003.
• Accepted October 28, 2003.

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