High-dose influenza vaccination and mortality among predominantly male, white, senior veterans, United States, 2012/13 to 2014/15

Introduction: It is unclear whether high- dose influenza vaccine (HD) is more effective at reducing mortality among seniors. Aim: This study aimed to evaluate the relative vaccine effectiveness (rVE) of HD. Methods: We linked electronic medical record databases in the Veterans Health Administration (VHA) and Medicare administrative files to examine the rVE of HD vs standard- dose influenza vaccines (SD) in preventing influenza/pneumonia-associated and cardiorespiratory mortality among VHA-enrolled veterans 65 years or older during the 2012/13, 2013/14 and 2014/15 influenza seasons. A multivariable Cox proportional hazards model was performed on matched recipients of HD vs SD, based on vaccination time, location, age, sex, ethnicity and VHA priority level. Results: Among 569,552 person-seasons of observation, 207,574 (36%) were HD recipients and 361,978 (64%) were SD recipients, predominantly male (99%) and white (82%). Pooling findings from all three seasons, the adjusted rVE estimate of HD vs SD during the high influenza periods was 42% (95% confidence interval (CI): 24-59) against influenza/pneumonia-associated mortality and 27% (95% CI: 23-32) against cardiorespiratory mortality. Residual confounding was evident in both early and late influenza periods despite matching and multivariable adjustment. Excluding individuals with high 1-year predicted mortality at baseline reduced the residual confounding and yielded rVE of 36% (95% CI: 10-62) and 25% (95% CI: 12-38) against influenza/pneumonia-associated and cardiorespiratory mortality, respectively. These were confirmed by results from two-stage residual inclusion estimations. Discussion: The HD was associated with a lower risk of influenza/pneumonia-associated and cardiorespiratory death in men during the high influenza period.