Post Hoc Analysis of PROGRESS: Evaluating the Safety of Atogepant in Participants With Chronic Migraine and Cardiovascular Risk Factors
Patricia Best1, Andrea Harriott2, Teshamae Monteith3, Cristina Tassorelli4, Stephanie Nahas5, Yingyi Liu6, Brett Dabruzzo6, Rosa De Abreu Ferreira6, Jonathan H. Smith6
1Mayo Clinic, 2Massachusetts General Hospital, 3University of Miami, 4University of Pavia, 5Thomas Jefferson University, 6AbbVie
Objective:
Evaluate the safety of atogepant in PROGRESS trial participants with chronic migraine (CM) and cardiovascular risk factors (CV-RFs).
Background:
Migraine is associated with cardiovascular disease (CVD) and CV-RFs.
Design/Methods:
A 12-week, international, randomized, double-blind, placebo-controlled phase 3 trial (PROGRESS; NCT03855137) enrolled participants (18-80 years) with ≥1-year CM (≥15 monthly headache days [MHDs] for 3 months before screening; ≥15 headache days [≥8 migraine days] during the 4-week screening period). Participants treated with atogepant 30mg twice-daily, 60mg daily, or placebo were stratified by 0, 1, or ≥2 baseline CV-RFs. CV-RFs included age (men: ≥45; women: ≥55), smoking, body mass index (BMI) ≥25kg/m2, hypertension, diabetes, dyslipidemia, sleep apnea, concomitant CVD or diabetes medicines, and history of stroke, myocardial infarction, transient ischemic attack, or peripheral arterial disease. CV treatment-emergent adverse events (TEAEs) were assessed.
Results:
Of 773 participants, 518 (1 missing data) comprised the pooled atogepant group (0 CV-RFs: 110[21.2%]; 1 CV-RF: 146[28.2%]; ≥2 CV-RFs: 261[50.4%]) and 255 comprised the placebo group (0 CV-RFs: 47[18.4%]; 1 CV-RF: 92[36.1%]; ≥2 CV-RFs: 116[45.5%]). Among all participants, the majority had ≥2 CV-RFs compared to 0 or 1 CV-RFs. At baseline, participants with ≥2 CV-RFs had higher mean age, BMI, and MHDs versus those with 0 or 1 CV-RFs. Most common CV-RFs were dyslipidemia (47.6%), BMI ≥25kg/m2 (43.1%), and hypertension (40.9%). CV-TEAEs occurred at low frequencies among participants with ≥2 CV-RFs (placebo: 3/116[2.6%]; pooled atogepant: 9/261[3.4%]), and none were serious. Treatment-related CV-TEAEs included palpitations (n=2) and increased blood pressure (n=1) in the pooled atogepant group (all 30mg twice-daily) and flushing (n=1) in the placebo group. Palpitations led to 1 discontinuation (assessed as not treatment-related) in the pooled atogepant group.
Conclusions:
This post hoc analysis demonstrates that CV-TEAEs occurred at low frequencies among atogepant-treated participants with CM and CV-RFs. All CV-TEAEs were nonserious, most were not treatment-related, and only 1 led to discontinuation.