Statin Treatment Options during vaccination against inFLUenza (STOPFlu) : a observational study of the interaction between statins and influenza vaccination

Date of Approval
Application Number
21_000554
Technical Summary

Background

Influenza vaccination is routinely advised for many at-risk groups including adults agedā‰„65 years and, and younger patients with diabetes and cardiovascular disease. Many of these patients are also likely to be prescribed statins for control of cardiovascular risk. However, the mechanism by which statins protect against heart disease may inhibit the immune response to vaccination, potentially lowering its efficacy. This is further complicated by statins themselves potentially offering some protection against influenza. Robust evidence is needed to guide clinical practice and ensure vaccine response is maximised.

Objectives

To evaluate the potential modifying effect of statins on the effectiveness of the influenza vaccine and as a prophylaxis against influenza.

Methods

Annual cohorts of patients eligible for the influenza vaccine will be selected from 2010-20. Our primary analysis will test for an association between statin use and influenza outcomes, amongst patients receiving the influenza vaccine. Secondary analyses will estimate influenza vaccine effectiveness separately among statin users and nonusers, and the extent of any prophylactic effect of statins. A composite influenza outcome will be primary-care consultations for influenza-like illness and hospital admissions for influenza. Cox regression will be used to model the time to influenza with weighting by propensity scores to adjust for confounders observed in the data. We anticipate residual bias from unmeasured confounders so will apply a before-and-after quasi-experimental study design, the prior event rate ratio method, to adjust for this. We shall evaluate any remaining residual bias, applying the analysis protocol to a negative control outcome, such as shingles, for which we expect no association with influenza vaccination. Since polypharmacy is likely to be prevalent in frail and older populations, further sensitivity analysis will screen the five other most common medications to assess the extent to which any observed interaction effect may be attributable to other, concomitantly prescribed medications.

Health Outcomes to be Measured

Composite outcome: hospital admissions for influenza; consultations in primary care for symptoms consistent with influenza-like illness
Negative control outcome: shingles

Collaborators

Adam Streeter - Chief Investigator - University of Exeter
Adam Streeter - Corresponding Applicant - University of Exeter
- Collaborator -
Andrea Shelly - Collaborator - University of Exeter
Lauren rodgers - Collaborator - University of Exeter
Sarah Walker - Collaborator - University of Exeter
William Hamilton - Collaborator - University of Exeter
William Henley - Collaborator - University of Exeter

Linkages

HES Accident and Emergency;HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation