Lipid-Lowering Medications Increase the Severity of Hymenoptera Venom Anaphylaxis

BACKGROUND: Platelet-activating factor (PAF), a key mediator of anaphylaxis, is inactivated by PAF-acetylhydrolase (PAF-AH). Platelet-activating factor-AH circulates complexed to low-density lipoprotein. Lipid-lowering medications interfere with PAF inactivation by lowering the concentration of low-density lipoprotein-PAF-AH complex, but their effect on anaphylaxis severity is unknown. OBJECTIVE: To determine whether use of lipid-lowering medication alters anaphylaxis severity. We hypothesized that use of lipid-lowering medication would increase the risk of severe anaphylaxis. METHODS: This is a retrospective chart review of patients from Canada, United States, and Germany, assessed between 2010 and 2023 for multisystem reactions to insect stings. Logistic regression examined the association between lipid-lowering medication use and anaphylaxis severity (mild to moderate vs severe). Multivariable analyses adjusted for age, sex, β-blocker, angiotensin-converting enzyme inhibitor, respiratory disorders, and mastocytosis/hereditary α-tryptasemia. RESULTS: Among the 778 total patients, 111 (14%) were taking lipid-lowering medications. Lipid-lowering medication use was associated with increased odds of severe anaphylaxis in multivariable analysis (adjusted odds ratio [aOR] = 2.0; 95% CI, 1.3-3.1; P = .0036). The association remained significant among 518 patients with Hymenoptera allergy confirmed by skin and/or serum tests (aOR = 2.0; 95% CI, 1.2-3.5; P = .012). In a sensitivity analysis substituting baseline tryptase for mastocytosis/hereditary α-tryptasemia among patients with available measurements (n = 197), the association was directionally consistent but not statistically significant (aOR = 1.9; 95% CI, 0.9-3.8; P = .092). CONCLUSIONS: Lipid-lowering medication use was associated with increased anaphylaxis severity in the primary analysis and confirmed-allergy cohort. Patients receiving lipid-lowering medications may be at higher risk for severe reactions, and clinicians should consider risk mitigation strategies, including venom immunotherapy (eg, modified buildup protocols, extended treatment duration), ready access to self-administered epinephrine, and multidisciplinary care.