Clinical Edge

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Risks in Patients with Migraine Receiving Prophylaxis

In a cohort study of patients with migraine receiving prophylactic treatments, increased risk of cardiovascular (CV) and cerebrovascular events and mortality were observed. However, treatments other than topiramate likely represent markers for outcome risk factors that developed or progressed after cohort entry, rather than being a direct effect of the treatments. Patients with migraine aged 18-65 years were identified from 2010 - 2015. Topiramate initiators during follow-up were propensity score-matched separately to anticonvulsant, cardiovascular treatment, antidepressant, and other prophylactic treatment initiators. Researchers found:

  • 119,243 patients with migraine were included in the final cohort.
  • The matched topiramate initiators had a lower mortality risk vs antidepressant and anticonvulsant initiators.
  • In a case-control analysis, increased risks of several outcomes were observed with all prophylactic treatments relative to nonuse of that treatment, expect for topirmate and calcium channel blockers.


Hoffman V, et al. Risk of cardiovascular and cerebrovascular events and mortality in patients with migraine receiving prophylactic treatments: An observational study. [Published online ahead of print June 13, 2019]. Cephalalgia. doi: 10.1177/0333102419856630.


This was a large complex, observational cohort study with a rigorous statistical analysis plan, optimally executed. The most important finding was negative, that non-fatal vascular events did not occur in preventive medication initiators more than those not starting prophylaxis and did not differ from what had previously been demonstrated by Dr. Tobias Kurth and colleagues in other analyses. That said, there were 2 contradictory associations with topiramate use. Overall, the initiation of topiramate preventive therapy seemed to be associated with lower mortality rates than other prophylaxis such as antidepressants and AEDs. However, 3 months of topiramate use was associated with a higher risk of TIA than similar migraine patients taking no topiramate for 3 months. The authors speculated that topiramate might be associated with risk factors for TIAs. Further studies will need to zero in on this question, as well as whether other manageable patient features might correlate with better associations and therefore more treatable predictors for vascular risk. Stewart J. Tepper, MD, FAHS, Professor of Neurology, Geisel School of Medicine at Dartmouth, Director, Dartmouth Headache Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH