Triptans and Ergotamines: What’s the CV Risk?

Use of migraine-specific drugs is limited mainly by underlying cardiovascular (CV) disease or risk factors for such. Vasoconstriction caused by triptans and ergotamines is rare, but can increase the risk of serious ischemic events. The rarity of such events makes them difficult to assess in randomized controlled trials. Post-marketing observational studies provide some information on this issue.

Ergotamine and dihydroergotamine: First specific anti-migraine agents, introduced in 1926 and 1945, respectively. Affinity for central 5HT1 b/d receptors: Inhibits neurogenic inflammation caused by cerebral vasoconstriction. Activation of other 5HT receptors and alpha adrenoreceptors: Linked to rare side effects such as potentially fatal vasospastic reactions.

Sumatriptan: First selective 5HT1 b/d receptor agonist, developed in the early 1990s . Six more sumpatriptan analogs have been licensed in the past 2 decades: No major CV issues reported in RCTs of these agents; post-marketing reports: Serious ischemic events have been reported; amount of risk and causal relationships remain elusive.

A systematic review of 4 observational studies published between 2004 and 2007 looked at CV outcomes and intensity or recency of ergotamine and/or triptan use. Results were published in Cephalalgia in March 2015. Roberto G, Raschi E, Piccinni C, et al. Adverse cardiovascular events associated with triptans and ergotamines for treatment of migraine: systematic review of observational studies. Cephalalgia. 2015;35:118-131.

Intense use: Linked to over 2-fold increased risk of serious ischemic events (Pooled OR from 2 studies 2.28 [95% CI, 1.18-4.41]).Concomitant use with CV medications may increase risk of serious ischemic events by 8-fold.(2) Recent use: Not significantly associated with various CV events (MI, stroke, serious ventricular arrhythmia, unstable angina, TIA).(3)

Intense use: No increased risk of serious ischemic events, although no firm conclusions can be drawn (Pooled OR from 3 studies 0.86 [95% CI, 0.52-1.43]). Recent use: Findings on stroke risk conflicting, but if the risk exists it may be small (2 studies: OR 0.90 [95% CI, 0.64-1.26] and 2.51 [1.10-5.7]; results not pooled because of high heterogeneity): One study suggested triptans are not significantly associated with various CV outcomes (MI, stroke, serious ventricular arrhythmia, unstable angina, TIA).(3) Another showed over 2-fold increased risk of stroke for triptan users compared with nonusers with migraine.(4)

“Very low” quality data exists about the risk for rare but serious CV events with ergotamine and triptan use.(1) Few comparative observational studies have looked at this issue in “real-world” settings. Consider: Patients’ baseline CV risk before prescribing triptans or other first-line therapies such as NSAIDs or paracetamol. Educate: Patients who are using ergotamines that intense use could increase the risk of serious ischemic events, especially among those with elevated CV risk.