Noah Rosen, MD
Results of a 6-month treatment trial pooling data from the EVOLVE‐1, EVOLVE‐2, and REGAIN studies suggest that the cardiovascular safety of galcanezumab (Emgality, Eli Lilly) is good, with little difference between those treated with the calcitonin gene-related peptide (CGRP) inhibitor and those administered placebo.

In this analysis, the frequency of any cardiovascular treatment-emergent adverse event (AE), broad or narrow term, was ≤1.4%. Those treated with 120-mg and 240-mg galcanezumab experienced ≥1 cardiovascular AE at rates of 2.6% (odds ratio [OR], 0.9; 95% CI, 0.5–1.5) and 3.3% (OR, 1.1; 95% CI, 0.7–1.9), respectively, similar to the placebo rate of 2.9%.

“In this 6‐month treatment trial, the percentages of galcanezumab‐ and placebo‐treated patients that reported CV TEAEs or serious adverse events were low and similar between groups with few discontinuations,” the investigators detailed. “Thus, no clinically meaningful treatment group differences were observed for changes in BP, pulse, or ECG parameters. Additional longer‐term studies in a broader and larger cohort are required to better characterize CV safety.”

As well, they importantly noted that only 8 (0.01%) of the patients in the study had known cardiovascular disease, thus these findings are not adequate to determine the anti-CGRP agent’s safety in those with a past history of ischemic events.

The investigators, including Noah Rosen, MD, program director of neurology at the Zucker School of Medicine, Northwell Health, explored the cardiovascular outcomes of 2 similarly designed, 6-month studies of galcanezumab in patients with chronic migraine as well as a third 3-month study. In total, the data included 2886 patients randomized 1:1:2 to either 120 mg (n = 705) or 240 mg (n = 730) galcanezumab, or placebo (n = 1451).

The study group consisted of 1773 patients with episodic migraine (galcanezumab 120 mg, n = 432; galcanezumab 240 mg, n = 448; placebo, n = 893) and 1113 patients with chronic migraine (galcanezumab 120 mg, n = 273; galcanezumab 240 mg, n = 282; placebo, n = 558).

As well, 18.5% of placebo‐treated and 17.2% of galcanezumab‐treated patients were noted as having cardiovascular disease risk, with the most common conditions (≥5%) related to hypertension, dyslipidemia, and hyperglycemia/new‐onset diabetes mellitus. Cardiovascular concomitant medications were similar across groups, with antihypertensives the most often used (8.8% placebo and 6.7% galcanezumab).

Similar to the larger assessment, the percentage of patients with ≥1 likely cardiovascular AE, in narrow terms only, in the cardiovascular disease risk subgroup was 4.1% for placebo, compared to 1.6% and 3.2% for the galcanezumab 120-mg and 240-mg groups, respectively.

“In the overall safety population, the lack of dose increases in cardiovascular medications or initiation of new cardiovascular medication provides additional evidence that galcanezumab did not have a negative impact on cardiovascular function,” Rosen and colleagues wrote. “While the frequency of cardiovascular medication increases was higher in the CV disease risk subgroup ‘yes,’ compared to the ‘no’ subgroup, the frequency was similar between galcanezumab and placebo within each subgroup.”

Ultimately, serious AEs which were cardiovascular-related occurred in the 3 patients in the galcanezumab 240 mg group—an acute myocardial infarction, a pulmonary embolism, and a transient ischemic attack—and 3 in the placebo group—a pulmonary embolism, deep vein thrombosis, and a myocardial infarction—though none were considered treatment-related.

Discontinuations occurred rarely, with only 4 placebo patients and 1 treated with the study drug doing so due to a cardiovascular-related AE.

Least squares mean and categorical changes from baseline in blood pressure (BP), pulse, and QT interval corrected using Fridericia's correction were similar across treatment groups. The mean change difference in diastolic BP was statistically significant between the placebo group and the galcanezumab 240-mg group (−0.8 mm Hg; P = .018), though the magnitude of change was small, at <1 mm Hg, and Rosen and colleagues reported a greater mean decrease in galcanezumab compared to placebo.

“In conclusion, the data from this integrated analysis do not suggest that galcanezumab treatment in patients with migraine resulted in hemodynamic changes consistent with vasoconstriction or an increase in cardiovascular adverse events, including those related to ischemia up to 6 months of treatment,” Rosen and co. concluded. “Longer-term studies in larger numbers of patients are needed to fully assess cardiovascular safety, particularly for rare events.”
REFERENCE
 Oakes TM, Kovacs R, Rosen N, et al. 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. Headache. Published online November 13, 2019. doi: 10.1111/head.13684.