Flu Shot Linked to Heart Failure Survival Influenza Vaccine in Heart Failure: Cumulative Number of Vaccinations, Frequency, Timing, and Survival: A Danish Nationwide Cohort Study

Patients with heart failure (HF) who receive influenza vaccination may be at a lower risk of both all-cause mortality and cardiovascular death after adjustment for confounders, according to a large-scale observational nationwide study of Danish citizens. “Annual influenza vaccination may be an effective treatment strategy to improve survival in heart failure,” lead author Daniel Modin (Department of Cardiology, Herlev & Gentofte Hospital, Denmark), and colleagues wrote in their paper recently published in Circulation.

Influenza vaccination for patients with heart failure has been recommended by contemporary guidelines by cardiac societies and health authorities without a class of recommendation or level of evidence due to the lack of sufficient data from randomized trials.  The study by Modin and colleagues, the largest cohort study thus far, therefore sought to investigate whether the frequency, cumulative number, and timing of flu shots may grant survival benefits in HF patients. For the study, Modin et al. identified 134,048 patients in Denmark newly diagnosed with new HF in the period from January 1, 2003, to June 1, 2015.  Flu vaccination rates ranged from 16% in 2003 to 52% in 2015 with a peak of 54% in 2009.  Patients were followed for a median follow-up of 3.7 years (all-cause death) and 3.3 years (cardiovascular death).  Among those, patients who received ≥1 vaccination (58%) were slightly older, more frequently male, more likely to be vaccinated before the HF diagnosis, and displayed a higher prevalence of comorbidities and medication use.

In unadjusted analysis, HF patients receiving ≥1 influenza vaccinations were associated with a higher risk of all-cause death (hazard ratio [HR], 1.28; 95% CI, 1.26–1.30; P<0.001) and cardiovascular death (HR, 1.26; 95% CI, 1.23–1.28; P<0.001). However, after accounting for all identified confounders (such as prescriptions, health conditions, household income, education, and inclusion date), vaccination was associated with an 18% reduction of both all-cause mortality and cardiovascular mortality (HR, 0.82; 95% CI, 0.81–0.84; P<0.001).

Moreover, the cumulative number of vaccines was significantly associated with a reduced risk of all-cause and cardiovascular death (P for trend <0.001).  A vaccination frequency of 0 to 1 per year reduced the risk of all-cause death by 13% and cardiovascular death by 8%.  Annual flu vaccination has been regarded as a safe, low-cost way to reduce flu-related deaths and complications and is routinely recommended for patients with histories of heart disease and stroke. The timing and frequency of flu shots mattered.  Getting a flu shot earlier in the flu season (September-October vs. November-December) was associated with a greater reduction in cardiovascular and all-cause mortality. Furthermore, patients who received flu vaccination less than once per year but more than not at all had a lower mortality rate than the unvaccinated individuals.

“However, we had information only on vaccines administered by general practitioners,” the investigators noted.  Furthermore, we lacked data on important clinical variables such as left ventricular ejection and brain natriuretic peptide levels. In addition, the Danish National General Practitioners Reimbursement Registry used to assess the exposure to influenza vaccination in this study has not been previously validated.” They also remarked, “Influenza vaccination should be considered as a potential treatment strategy comparable to other medical treatments such as β-blockers and angiotensin-converting enzyme inhibitors to improve survival in heart failure.” They added that emphasizing this in future heart failure guidelines would encourage vaccination of patients with heart failure and likely improve patient survival.