Influenza Vaccination in Patients With Chronic Heart Failure: The PARADIGM-HF Trial

JACC Heart Fail. 2016 Feb;4(2):152-158. doi: 10.1016/j.jchf.2015.10.012. Epub 2015 Dec 30.


Objectives: This study sought to examine the prevalence and predictors of influenza vaccination among participants in the PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) study and investigate associations between receiving influenza vaccine and cardiovascular death or heart failure hospitalizations, all-cause hospitalizations, and cardiopulmonary or influenza-related hospitalizations.

Background: Influenza is associated with an increased risk for cardiovascular events in patients with heart failure.

Methods: We used data from the PARADIGM-HF trial in which patients with heart failure were randomized to the angiotensin receptor neprilysin inhibitor LCZ696 (sacubitril/valsartan) or enalapril. We assessed predictors of receiving influenza vaccination, and examined the relationship between influenza vaccination and outcomes in a propensity-adjusted model.

Results: Of 8,099 study participants, 1,769 (21%) received influenza vaccination. We observed significant regional variation in vaccination rates, with highest rates in the Netherlands (77.5%), Great Britain (77.2%), and Belgium (67.5%), and lowest rates in Asia (2.6%), with intermediate rates in North America (52.8%). Top predictors of vaccination included enrolling country, white race, implanted defibrillator, older age, lower New York Heart Association functional class, lower heart rate, and a history of diabetes mellitus. Influenza vaccination was associated with a reduced risk for all-cause mortality in propensity-adjusted (hazard ratio: 0.81; 95% confidence interval: 0.67 to 0.97; p = 0.015) models.

Conclusions: Influenza vaccination rates varied widely in patients with heart failure with reduced ejection fraction enrolled in the PARADIGM-HF trial, and vaccination was associated with reduced risk for death, although whether this association was causal cannot be determined.

Keywords: chronic heart failure; clinical trial; influenza vaccination.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Double-Blind Method
  • Europe / epidemiology
  • Female
  • Heart Failure / complications
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Humans
  • Influenza A virus / immunology*
  • Influenza Vaccines / administration & dosage*
  • Influenza, Human / complications
  • Influenza, Human / prevention & control*
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Survival Rate / trends
  • United States / epidemiology
  • Vaccination / methods*


  • Influenza Vaccines