Statins may modulate the effectiveness of the flu vaccine according to the type of respiratory outcome: Results from the Statin Treatment OPtions during vaccination against inFLUenza (STOPFlu) study

Background: Influenza (flu) vaccination is routinely advised for adults aged≥65 years. Many of these patients are also likely to be prescribed statins for control of cardiovascular risk. Previous studies have suggested that statin use may reduce the effectiveness of flu vaccination, although these may have been susceptible to bias from unobserved sources.

Objectives: We report findings from the STOPFlu study investigating the potential modifying effect on flu vaccination from concomitant statin use. The study uses a new-user quasi-experimental design to adjust for confounding bias from observed and unobserved sources. We compare the results from annual cohorts by severity of outcome.

Methods: We recruited cohorts of vaccinated adults aged≥65y from primary care practices registered to the UK Clinical Practice Research Datalink for each year from 2010 to 2018 and compared new statin users to statin-free patients. The primary outcome was a composite of acute respiratory infection (ARI) diagnosed in primary care and hospital admissions for ARIs. These included influenza-specific diagnoses and diagnoses of pneumonia, which we analysed separately as secondary outcomes. We estimated the impact of statin use on vaccine effectiveness using the Prior Event Rate Ratio (PERR) method. This approach involved use of a statin-free prior period from the vaccinated cohorts to measure both observed and unobserved confounding bias.

Results: The adjusted hazard ratios (HR) for the risk of general ARI were mostly non-significant, varying from 0.92 (95%CI 0.86, 0.99) in 2010 to 1.00 (95%CI 0.92, 1.10) in 2018. Based on the baseline risk in 2010, this was equivalent to preventing 7 fewer cases for every 1000 new statin users. The HRs for flu were less precise due to sparsely coded outcomes, and varied from 0.89 (95%CI 0.56, 1.36) in 2018 to 1.21 (95%CI 0.82, 1.86) in 2013 (aggregate estimate: HR 1.05 95% CI 0.91-1.20). The HRs for pneumonia varied from 0.49 (95%CI 0.42, 0.58) in 2011 to 0.73 (95%CI 0.61, 0.87) in 2018. Based on the baseline risk in 2018, this was equivalent to preventing at least 23 cases for every 1000 new statin users.

Conclusions: After adjustment for unmeasured confounding, initiation of statins was not associated with vaccine effectiveness for influenza outcomes but the point estimate was consistent with previous studies showing a modest reduction in effectiveness on statin therapy. In contrast, taking statins was associated with improved vaccine effectiveness for the more severe pneumonia outcome. This may reflect a beneficial effect of statins on vaccine response or an immunomodulatory effect of statins at the time of potential pneumonia infection.