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Could Influenza Vaccination Prevent More Than Just the Flu?

Influenza vaccination may reduce cardiac-related hospital admissions and all cause mortality in patients with diabetes.

Currently, only low-quality evidence exists to support efficacy of influenza vaccination to prevent seasonal influenza in patients with diabetes. There is even less information regarding the impact of influenza vaccination on cardiovascular events or all-cause mortality in this population. A recent study published in the Canadian Medical Association Journal was designed to evaluate the impact of seasonal influenza vaccination on admission to the hospital for acute myocardial infarction, stroke, heart failure, or pneumonia, and all-cause mortality in patients with type 2 diabetes.

Conducted over a 7-year time period from 2003 – 2009, the study analyzed retrospective patient data from the Clinical Practice Research Datalink in England. The analysis included 124,503 adult patients diagnosed with type 2 diabetes. At baseline, characteristics such as age, sex, smoking status, BMI, cholesterol labs, HbA1c, blood pressure, medications, and comorbidities were compared between patient groups. Vaccination rates of the included participants ranged from 63.1% to 69.0% per year. In general, unvaccinated participants were younger, had lower rates of pre-existing comorbidities, and were taking fewer medications.

Four time periods in each cohort year were analyzed for outcomes including: pre-influenza, influenza season, post influenza, and summer. To account for less disease activity in the summer, effect estimates were adjusted for residual confounding. The statistical outputs included an unadjusted analysis (focused solely on vaccination status as the predictor) and an adjusted analysis (including adjustment for study covariates and seasonal residual confounding). The study focused on comparing rates of hospitalizations for cardiac outcomes, including acute myocardial infarction, stroke, and heart failure as well as pneumonia or influenza and all-cause mortality. An incidence rate ratio (IRR) was calculated for each outcome by comparing rates of the specified cardiovascular event between vaccinated and unvaccinated participants using Poisson regression.

In the unadjusted analysis, vaccine recipients had statistically significantly higher rates of hospitalization for acute myocardial infarction and heart failure, non-significant increases in stroke and pneumonia, and significantly lower rates of all-cause mortality during the influenza season. However, after adjustment for covariates and residual confounding, vaccination was associated with statistically significant reductions in hospital admission for stroke by 30% (IRR 0.70, 95% CI 0.53–0.91), heart failure by 22% (IRR 0.78, 95% CI 0.65–0.92), pneumonia or influenza by 15% (IRR 0.85, 95% CI 0.74–0.99) and all-cause mortality by 24% (IRR 0.76,95% CI 0.65–0.83) during influenza season among people with diabetes who were vaccinated compared with those who were unvaccinated. There was also a 19% reduction in the rate of hospital admissions for acute MI, which was not statistically significant (IRR 0.81, 95% CI 0.62–1.04). These outcomes did not persist during the pre- or post- influenza seasons.

The baseline characteristics of subjects enrolled in this retrospective analysis showed that sicker subjects received the flu vaccination more frequently. Given this observation, and seasonal confounding of flu outbreaks, data adjustments favored fewer cardiovascular events and lower rates of all-cause mortality during the influenza season spanning 7 years of data.  While other studies have shown that influenza vaccination can reduce the risk of cardiovascular events in high-risk patients, this study is the first to demonstrate a reduction in cardiovascular events associated with influenza vaccination in patients with diabetes. This study is notable for its large sample size and long duration. However, given the retrospective nature of the study, further trials are warranted to offer conclusive evidence about the benefits of influenza vaccination in patients with diabetes.

Practice Pearls:

  • Previous clinical trials aimed at studying the effectiveness of the flu vaccine in patients with diabetes are often small, inconclusive, and have not investigated cardiovascular outcomes.
  • When data was adjusted for baseline covariates and seasonal residual confounding, patients who received the influenza vaccination had significantly reduced rates of hospital admissions for stroke, heart failure, pneumonia or influenza, and all-cause mortality.
  • Large experimental or quasi-experimental trials are needed to establish a causal link between influenza vaccination and clinical endpoints in patients with diabetes.

References:

Vamos EP, Pape UJ, Curcin V, Harris DPhil MJ, Valabhji J, Majeed A, et al.  Effectiveness of the Influenza vaccine in preventing admission to hospital and death in people with type 2 diabetes.  CMAJ. 2016 July 25.

Remschmidt C, Wichmann O, Harder T. Vaccines for the prevention of seasonal influenza in patients with diabetes: systematic review and meta-analysis. BMC Med 2015;13:53.

Researched and prepared by Alysa Redlich, Pharm.D. Candidate, University of Rhode Island, reviewed by Michelle Caetano, Pharm.D., BCPS, BCACP, CDOE, CVDOE