Influenza Vaccine Associated With Reduced Risk of All-Cause Mortality in Heart Failure Patients

In an analysis of PARADIGM-HF participants, researchers discovered a possible all-cause mortality risk reduction in patients with heart failure who had received influenza vaccination.

Influenza vaccination was associated with a reduced risk of all-cause mortality in patients with heart failure (HF) in propensity-adjusted models, according to an analysis of participants from the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) clinical trial, published in JACC: Heart Failure.

In the original trial, patients with symptomatic HF with reduced ejection fraction were randomly allocated to receive either the angiotensin receptor neprilysin inhibitor LCZ696 (sacubitril/valsartan) or enalapril. Once enrolled, patients were queried about their influenza vaccination status in the past 12 months, and cardiopulmonary and influenza-related hospitalization data were recorded through case report forms.

Researchers of the present study assessed predictors of receiving influenza vaccination and the relationship between vaccination and outcomes in a propensity-adjusted model.

Of 8399 participants, 1769 received influenza vaccination (21%). Those who received the vaccine were typically older, had higher BMI, lower New York Heart Association functional class and estimated glomerular filtration rates, and were more likely to be male.

Vaccination was associated with a reduced risk for all-cause mortality in propensity-adjusted models (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.67-0.97; P=.015). However, vaccination was also associated with increased rates of cardiopulmonary, influenza-related, and all-cause hospitalization in unadjusted models, but not in propensity-adjusted models.

“There are limited data on influenza vaccination rates in patients with heart failure worldwide,” researchers noted. “Even in the United States, influenza vaccination rates in patients with heart failure have ranged from 25% to approximately 76%, depending on the population studied.”

The most important factor influencing vaccination was country: rates were lowest in Asia. Meanwhile, older age, white race, and concomitant diabetes were significant predictors of vaccination, possibly due to increased utilization or improved access to health care.

Researchers suggested that future studies examine associations between multiple year influenza vaccination and cardiovascular outcomes in patients with HF, particularly since the specific vaccine (eg, trivalent, high dose, quadrivalent) that may be most beneficial has yet to be identified.


Vardeny O, Claggett B, Udell JA, et al; for the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Investigators. Influenza vaccination in patients with chronic heart failure: the PARADIGM-HF trial. JACC Heart Fail. 2016;doi:10.1016/j.jchf.2015.10.012.