Abstract text (incl. figure legends and references)

Objective: ADVANCE (NCT03777059) was a phase 3, 12-week trial in episodic migraine participants. ADVANCE trial completers were eligible to roll over into a 40-week, open-label, extension trial (309-OLEX, NCT03939312). The objective was to evaluate safety of atogepant in participants with cardiovascular risk factors (CV-RFs) from ADVANCE and 309-OLEX.

Methods: Post-hoc analysis of participants receiving placebo or 60mg atogepant from ADVANCE and 309-OLEX trials were evaluated for CV-RFs: age [men ≥45 years; women ≥55 years], BMI ≥25 kg/m2, cardiovascular disease (CVD) [including history of myocardial infarction, stroke, or transient ischemic attack], diabetes, dyslipidemia, hypertension, sleep apnea, smoking; or taking concomitant medications for CVD, diabetes, or hypertension. (Goff et al. Circulation 2014;129:S49–S73) Participants were stratified into 3 groups: 0, 1, or ≥2 CV-RFs.

Results: Percentage of participants with 0, 1 or ≥2 CV-RFs were similar across treatment arms and trials (Table 1); 87% of ADVANCE and 88% of 309-OLEX participants treated with atogepant had at least 1 CV-RF. Most common CV-RFs in both trials included BMI ≥25 kg/m2 (73.9-74.1%), hypertension (35.6-38.6%) and dyslipidemia (36.9-37.9%). CV treatment-emergent adverse events (CV-TEAEs) were infrequent (<5%, Table 1). Treatment-related CV-TEAEs included atrioventricular block in 1 placebo participant (0.4%), and palpitations in 2 atogepant participants (one in each trial [0.1%-0.5%]). No CV serious adverse events (CV-SAEs) were observed in either trial (Table 1). Treatment emergent hypertension events were reported in 0.4% of atogepant participants and 0.5% of placebo participants in the ADVANCE trial, and in 1.6% of the 309-OLEX trial participants.

Conclusions: Participants with baseline CV-RFs were well represented in ADVANCE and 309-OLEX. Low incidence of CV-TEAEs were noted. These data provide evidence supporting the safety profile of atogepant, specifically in those with CV-RFs.