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No new cardiovascular safety concerns with long-term use of lasmiditan

Presented By
Dr H. Hochstetler
Conference
MTIS 2020
Trial
Phase 3, GLADIATOR

 

Lasmiditan is a selective 5-HT1F receptor agonist that lacks the vasoconstrictive activity associated with other acute treatments for migraine. In an interim analysis of the long-term GLADIATOR trial, no vasoconstriction-related cardiovascular events occurred during the lasmiditan treatment-emergent period [1].

Previous studies showed that lasmiditan is associated with a low risk of cardiovascular treatment-emergent adverse events (AEs), specifically palpitations and tachycardia. No difference in cardiovascular treatment-emergent AE frequency in subjects with or without cardiovascular risk factors was found.

Patients who previously participated in phase 3, placebo-controlled, single-attack lasmiditan studies could be enrolled in the open-label, randomised GLADIATOR trial. These included patients with cardiovascular risk factors, coronary artery disease, arrhythmia, and uncontrolled hypertension. Participants received 100 or 200 mg lasmiditan either as a single dose within 4 hours after pain onset or as 2 doses within 2-24 hours after pain onset. To assess the long-term cardiovascular safety of lasmiditan for the acute treatment of migraine for up to 1 year, interim results were analysed.

In total, 19,058 migraine attacks were treated. Study median duration was 288 days. A total of 81% of patients had ≥1 cardiovascular risk factor, 0.3% had coronary artery disease, and 35% had low high-density lipoprotein (HDL) cholesterol.

As some cardiovascular events were likely not reported as treatment-emergent or were identified later, cardiovascular AE rates were assessed during 3 different time periods:

  • treatment-emergent: <48 hours after the dose;
  • intermediate: 48 hours until 1 week after the dose; and
  • remote: >1 week after the dose.

No vasoconstriction-related cardiovascular events occurred in the treatment-emergent period. Such events were rarely observed; all were in the remote period, limiting clinical interpretation. Treatment-related cardiovascular events, specifically palpitations and tachycardia, were more frequent in the treatment-emergent period versus intermediate and remote periods. No cardiovascular safety concerns were identified during long-term use of lasmiditan, neither in patients with cardiovascular risk factors nor in elderly patients.

This interim analysis showed that no vasoconstriction-related cardiovascular events occurred during the lasmiditan treatment-emergent period. The cardiovascular safety of lasmiditan was generally consistent with data from single-attack studies.

 

  1. Hochstetler H. Long-term cardiovascular safety of lasmiditan for the acute treatment of migraine for up to one year: interim results of an open-label phase 3 study (GLADIATOR). MTIS Virtual Symposium 2020, abstract MTV20-DP-039.


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