Influence of Statins on Influenza Vaccine Response in Elderly Individuals

Abstract

Influenza vaccination strategies have targeted elderly individuals because they are at high risk of disease complications and mortality. Statins are a class of drugs used to treat hypercholesterolemia and are frequently used in the elderly population to reduce the risk of cardiovascular disease. However, statins are also known to have immunomodulatory effects that could impact influenza vaccine response. In a post hoc analysis, we performed a cross-sectional observational study nested within a comparative immunogenicity clinical trial of adjuvanted versus unadjuvanted influenza vaccine in elderly persons to evaluate the influence of statin therapy on the immune response to vaccination. Overall, data on >5000 trial participants were available for analysis. Comparison of hemagglutination-inhibiting geometric mean titers to influenza A(H1N1), A(H3N2), and B strains revealed that titers were 38% (95% confidence interval [CI], 27%-50%), 67% (95% CI, 54%-80%), and 38% (95% CI, 28%-29%) lower, respectively, in subjects receiving chronic statin therapy, compared with those not receiving chronic statin therapy. This apparent immunosuppressive effect of statins on the vaccine immune response was most dramatic in individuals receiving synthetic statins. These effects were seen in both the adjuvanted and unadjuvanted vaccine groups in the clinical trial. These results, if confirmed, could have implications both for future clinical trials design, as well as for vaccine use recommendations for elderly individuals.

Prevention and Control of Seasonal Influenza with Vaccines

“…A posthoc analysis of data from a randomized clinical trial comparing MF59-adjuvanted IIV3 and unadjuvanted IIV3 among persons aged ≥65 years demonstrated lower geometric mean titers following vaccination among persons receiving chronic statin therapy (by 38% [95% CI = 27-50] for A(H1N1), by 67% [95% CI = 54-80] for A(H3N2), and by 38% [95% CI = 28-49] for B). The effect was more pronounced among those receiving synthetic statin drugs (fluvastatin, atorvastatin, and rosuvastatin) relative to those receiving fermentation-derived statins (pravastatin, simvastatin, lovastatin, and Advicor) (213). A retrospective cohort study covering nine influenza seasons found reduced effectiveness of influenza vaccine against MAARI among statin users (214); however, this study did not evaluate confirmed influenza illness.…”

The Impact of Statin on Influenza Vaccine Efficacy in the Elderly and Patients With Acute Respiratory Illness

“…These effects were observed in both the adjuvanted and nonadjuvanted vaccine groups in the clinical trial. These results, if confirmed, could have implications both for future clinical trial designs, as well as vaccine use recommendations for the elderly (12). Also in another study, statin therapy was associated with reduced influenza VE against medically attended acute respiratory illness (MAARI).…”

“…The findings have potential implications for guidelines regarding statin use in older adults around the vaccination time, but additional studies, including researches examining laboratory-confirmed cases of flu, are needed to provide more guidance (12,13).…”

Design and rationale for the I nfluenza vaccination A fter M yocardial I nfarction (IAMI) trial. A registry-based randomized clinical trial

“…Moreover, statins may influence the vaccine response (28). In a recent observational study the antibody response to influenza vaccine was found to be significantly lower in elderly (>65 years) statin users compared with non-statin users (29). Blood samples are taken on two occasions; before vaccination and 4 weeks (+/-2-3 days) after vaccination.…”