The Flu Vaccine and Statins: A Conundrum?

Gayle Nicholas Scott, PharmD


February 18, 2016


Are statins protective against the flu, or do they reduce the efficacy of the flu vaccine?

Gayle Nicholas Scott, PharmD
Assistant Professor, Eastern Virginia Medical School, Norfolk, Virginia

A Protective Effect?

Research suggests that 3-hydroxy 3-methylglutaryl coenzyme A reductase inhibitors, or statins, have pleiotropic effects—that is, beneficial effects beyond the expected action of lowering cholesterol. Statins have been proposed to have antioxidant, anti-inflammatory, immunomodulatory, and antiproliferative effects, as well as the ability to stabilize plaque and inhibit platelet aggregation.[1]

The anti-inflammatory and immunomodulatory effects of statins have been proposed as a treatment basis for preventing and controlling influenza outbreaks.[2,3] However, observational research supporting this suggestion has been mixed.

Using data from the Centers for Disease Control and Prevention's Emerging Infections Program, which collects data on persons hospitalized with laboratory-confirmed influenza in 59 counties in 10 states, Vandermeer and colleagues[4] evaluated the association between receiving statins and influenza-related death for 3043 hospitalized adults during the 2007-2008 influenza season. Statin use was associated with reduced mortality in patients hospitalized with influenza (adjusted odds ratio, 0.59; 95% confidence interval [CI], 0.38-0.92).

One bias of this observational study results from so-called "healthy users"—a population made up of statin users who are likely to be more informed consumers of healthcare and who lead healthier lifestyles that could affect mortality.[5]

Canadian researchers[6] assessed the effect of statin use on hospitalization rates and mortality during the influenza season in a retrospective cohort study of 2.2 million patients aged 65 years or older over a 10-year period (1996-2006). Although the data showed statistically significant reductions in both hospitalization rates and mortality, the authors concluded that these effects could be attributed to confounding factors and that statins have a minimal protective effect against influenza morbidity.

Other epidemiologic research has not found any benefit of statins on influenza.[7,8] After adjustment for age, sex, obesity, and indication for statin, as well as unmeasured confounders, an association between statin use and influenza outcome was not observed. Prospective randomized controlled trials to determine the effect of statins on the morbidity and mortality of influenza have not been performed.

Effect on Vaccine Efficacy

Some researchers are concerned that the anti-inflammatory and immunomodulatory effects of statins could have a detrimental effect on the efficacy of the influenza vaccine.

Using a managed care database in Georgia, Omer and colleagues[9] conducted a retrospective cohort study over nine influenza seasons (2002-2011) to assess the effect of influenza vaccination and prescription statin status on medically attended acute respiratory illness (MAARI), a commonly used indicator of the population impact of influenza. Most patients were younger than 65 years. After adjustment for prespecified variables, statin therapy was associated with reduced effectiveness of the influenza vaccine against MAARI.

In a post hoc analysis of a randomized controlled trial[10] comparing the immunogenicity of adjuvanted vs unadjuvanted influenza vaccine in people aged 65 years or older, Black and colleagues[11] performed a cross-sectional observational study of 6961 study participants to evaluate the influence of statin therapy on the immune response to influenza vaccination. The titers of antibodies to influenza were substantially lower in persons taking statins. In statin users, titers to influenza A (H1N1) were 38% lower (95% CI, 27%-50%), titers to influenza A (H3N2) were 67% lower (95% CI, 54%-80%), and titers to B strains were 38% lower (95% CI, 28%-29%) than in nonusers, regardless of the vaccine type received (adjuvanted or unadjuvanted).

Statins, which have been shown to reduce cardiovascular mortality and major vascular events,[12,13] are among the most commonly prescribed medications in the world. In the United States, more than 40% of people who are older than 65 years use statins.[14] On the other hand, influenza is associated with considerable morbidity and mortality, especially in elderly persons, raising the question of benefit vs risk of statins in terms of possible reduced efficacy of the influenza vaccine.[15]

The current advice regarding statins and the influenza vaccine is to continue both preventive treatments.[16]

More research is needed to determine whether statins should be temporarily discontinued around the time of influenza vaccine administration and whether statins have any effect on influenza frequency or severity. Future vaccine research should be designed with consideration of potential effects of statins on vaccine titers.[2]


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