Starling, Amaal J.

Abstract Objective To assess cardiovascular (CV) safety of erenumab in clinical trial patients associated with degree of CV risk. Background Hypertension has been considered a theoretical risk associated with the inhibition of the calcitonin gene‐related peptide pathway in migraine management, particularly in a patient population with pre‐existing CV risk factors. Methods Data pooled from four double‐blind, randomized trials were used to assess blood pressure (BP) changes and CV safety in patients grouped based on 10‐year risk of cardiac, cerebrovascular, and peripheral artery disease as no‐risk‐factors, low‐risk (>0% to ≤10%), moderate‐risk (>10% to ≤20%), and high‐risk (>20%) categories. CV safety was assessed as ischemic cardiovascular and cerebrovascular adverse events (ICCAE). Results There was no apparent difference between placebo‐ ( N = 1032) and erenumab‐treatment groups (70 mg, N = 885; 140 mg, N = 504) in clinical worsening of BP category from baseline to Months 1–3 (14% [143/1032] placebo vs. 13% [114/885] and 14% [71/504] for erenumab 70 and 140 mg, respectively) regardless of baseline BP category. The adverse event (AE) profile of erenumab was similar across CV risk categories throughout the long‐term analysis. Erenumab‐treated patients with high and moderate 10‐year CV risk ( N = 107) did not experience any ICCAEs during the double‐blind treatment period; there was a single ICCAE (a cerebral dural venous sinus thrombosis) observed in the low‐risk erenumab group ( N = 273). There were no increases in AEs during the long‐term extensions of up to 5 years ( N = 2499; 3482 patient‐years of exposure to erenumab) with exposure‐adjusted incidence rates of cardio/cerebrovascular disorder AEs of 0.4, 0.5, 0.0, and 1.1 (per 100 patient‐years) for no risk factor ( N = 1805), low ( N = 492), moderate ( N = 121), and high ( N = 81) 10‐year CV risk groups, respectively. Conclusions Ischemic CV and cerebrovascular AEs were uncommon and the incidence rates were similar across the 10‐year CV risk categories. This analysis helps provide more detail on the CV safety of erenumab.