Cardiovascular safety of genetically proxied interleukin-5 inhibition: A mendelian randomization study

Interleukin-5 (IL-5) inhibitors have revolutionized the management of eosinophilic asthma. However, IL-5 is thought to play a protective role in atherosclerosis, and cardiovascular safety data for IL-5i are scarce. We used population-level data to examine the association between genetically proxied IL-5i and the risk of cardiovascular diseases. Genetic instruments for IL-5i were selected from a genome-wide association study of eosinophil count in 563,946 individuals. Genetic association data for coronary artery disease were obtained from 60,801 cases, 40,585 stroke cases, 7988 venous thromboembolism cases, and up to 406,111 controls. We used the inverse-variance weighted method and a series of sensitivity analyses. Nine genetic variants were selected to instrument IL-5i. Genetically proxied IL-5i was not associated with the risk of coronary heart disease (OR 0.82, 95%CI 0.65-1.03), stroke (OR 1.10; 0.95-1.27), or venous thromboembolism (OR 0.87; 0.64-1.17). We found no genetic evidence to suggest that IL-5i affects the risk of adverse cardiovascular and thromboembolic events.