Statin Therapy Reduces Influenza Vaccine Effectiveness, Studies Suggest

Two of the most used preventative health therapies—statins and the influenza vaccine—are especially common among the elderly, but new studies are hinting at the possibility that the former may reduce the efficacy of the latter.

Based on the new data, “my suggestion would be not to change any recommendations at this point,” said the primary investigator of one of the studies, Saad B. Omer, MBBS, MPH, PhD, of Emory University (Atlanta, GA). “On the other hand, it’s an extremely important area because flu is bad in older age groups and a lot of people use statins. It is extremely important to follow up on that signal.”

Both studies were published online October 28, 2015, in the Journal of Infectious Diseases.

More Acute Respiratory Illness with Statins

For their retrospective cohort study, Omer and colleagues looked at 137,488 patients treated within the Kaiser Permanente Georgia managed care organization over 9 consecutive influenza seasons between 2002 and 2011. About one-quarter of the population received the influenza vaccine and 21% were taking statins.

Most patients (91.9%) were older than 65 years. Those receiving both statins and the influenza vaccine had the highest prevalence of COPD (30.1%), cerebrovascular disease (42.7%), diseases of the circulatory system (80.2%), and diabetes (46.1%).

As a measure of vaccine effectiveness, investigators looked at all instances of medically attended acute respiratory illness (MAARI). During periods of both widespread and local influenza outbreaks, those taking statins were more likely to report acute respiratory illness than nonusers. After adjusting for confounders, vaccine effectiveness among statin users was still lower than nonusers during widespread influenza (12.6% vs 26.2%; mean difference 18.4%; 95% CI 2.9%-36.2%), but this difference merely trended during local outbreaks.

In a sex-specific analysis, vaccine effectiveness was observed to be similarly lower in both men and women taking statins compared with nonusers.

Lower Immunogenicity with Chronic Statins

In the second study, Steven Black, MD, of Cincinnati Children’s Hospital (Cincinnati, OH), and colleagues compare the safety and immunogenicity of 2 trivalent inactivated iinfluenza vaccines—an adjuvanted and an unadjuvanted version—among more than 5,000 patients older than 65 years treated during the 2009-2010 and 2010-2011 seasons in Colombia, Panama, the Philippines, and the United States.

About three-quarters of patients receiving each vaccine were taking fermentation-derived statins (eg, pravastatin, simvastatin, lovastatin, and Advicor), while the rest were on synthetic statins (eg, fluvastatin, atorvastatin, and rosuvastatin).

Those on chronic statin therapy had 38% to 67% lower titers of antibodies against 3 different influenza strains (A-H1N1, A-H3N2, and B) than nonusers, “indicating a marked apparent reduction in immunogenicity in statin recipients for all 3 antigens despite adjustment for age, high-risk group status, pretiter, and type of vaccine received,” write Black and colleagues.

The findings were magnified in individuals receiving synthetic vs fermentation-derived statins.

Identifying a Signal

Despite various confounders present in both studies, Robert L. Atmar, MD, and Wendy A. Keitel, MD, of Baylor College of Medicine (Houston, TX), write that “the findings that statin use adversely affects [inactivated influenza vaccine] immunogenicity and [vaccine effectiveness] are biologically plausible, based on known immunomodulatory effects of these drugs,” in an accompanying editorial.

While the results should not yet change clinical practice, they say, they “should be viewed as hypothesis generating and should prompt further investigations into whether statins reduce [vaccine] immunogenicity.”

A “major challenge” going forward will be to reduce potential confounders in future study designs, Atmar and Keitel say. They suggest using randomization to test the effects of delaying statin therapy in relation to vaccine administration or studying higher-dose alternatives.

Omer said the next set of studies should use PCR-confirmed influenza instead of MAARI as a marker of effectiveness “because not all of MAARI is caused by influenza.”

“This is how science evolves,” Omer told TCTMD. “You identify a signal. Then you do studies informed by that science. Then you change recommendations.”

Sources: 
1. Black S, Nicolay U, Del Giudice G, Rappuoli R. Influence of statins on influenza vaccine response in elderly individuals. J Infect Dis.2015; Epub ahead of print.
2. Omer SB, Phadke VK, Bednarczyk RA, et al. Impact of statins on influenza vaccine effectiveness against medically attended acute respiratory illness. J Infect Dis.2015; Epub ahead of print.
3. Atmar RL, Keitel WA. Influenza vaccination of patients receiving statins: where do we go from here [editorial]? J Infect Dis.2015; Epub ahead of print.

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