Evaluation of Cardiovascular Outcomes in Adult Patients With Episodic or Chronic Migraine Treated With Galcanezumab: Data From Three Phase 3, Randomized, Double-Blind, Placebo-Controlled EVOLVE-1, EVOLVE-2, and REGAIN Studies.

OBJECTIVE: Blood pressure (BP), pulse, electrocardiogram (ECG), and clinical cardiovascular (CV) outcomes in patients with episodic or chronic migraine treated for up to 6 months with galcanezumab compared to placebo were evaluated. BACKGROUND: Calcitonin gene-related peptide, a potent microvascular vasodilator, has a hypothesized protective role in CV health. Increased CV risks have been reported in patients with migraine. METHODS: In 2 similarly designed episodic migraine 6-month studies and 1 chronic migraine 3-month study, data from patients randomized (1:1:2) to subcutaneous injection of galcanezumab 120 mg/month (following initial 240 mg loading dose) or 240 mg/month or placebo were pooled. Treatment comparisons for cardiovascular treatment-emergent adverse events (CV TEAE) and categorical and mean changes in BP, pulse, and ECG were evaluated using the Cochran-Mantel-Haenszel test. Mean changes from baseline in BP, pulse, and ECG were evaluated using the analysis of covariance model. RESULTS: Overall, among galcanezumab 120 mg (n = 705) and 240 mg (n = 730), and placebo (n = 1451) groups, the percentage of patients reporting >/=1 CV TEAE was low and was similar between the galcanezumab 120 mg (2.6%; odds ratio [OR] = 0.9; 95% confidence interval [CI]: 0.5,1.5) and galcanezumab 240 mg (3.3%; OR = 1.1; 95% CI: 0.7,1.9), and placebo (2.9%) groups. The frequency of any individual CV TEAE, broad or narrow term, was