Author + information
- Received September 2, 2015
- Revision received October 22, 2015
- Accepted October 31, 2015
- Published online February 1, 2016.
- Orly Vardeny, PharmD, MSa,
- Brian Claggett, PhDb,
- Jacob A. Udell, MDc,
- Milton Packer, MDd,
- Michael Zile, MDe,
- Jean Rouleau, MDf,
- Karl Swedberg, MDg,h,
- Akshay S. Desai, MD, MPHb,
- Martin Lefkowitz, MDi,
- Victor Shi, MDi,
- John J.V. McMurray, MDj,
- Scott D. Solomon, MDb,∗ (, )
- PARADIGM-HF Investigators
- aPharmacy Practice Division, University of Wisconsin School of Pharmacy, Madison, Wisconsin
- bCardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts
- cDivision of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital and Women's College Hospital, Toronto, Ontario, Canada
- dDepartment of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas
- eMedical University of South Carolina and Ralph H. Johnston Veterans Administration Medical Center, Charleston, South Carolina
- fInstitut de Cardiologie, Université de Montréal, Montreal, Quebec, Canada
- gDepartment of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
- hNational Heart and Lung Institute, Imperial College London, London, England
- iNovartis Pharmaceuticals Corporation, East Hanover, New Jersey
- jBritish Heart Foundation Cardiovascular Research Center, University of Glasgow, Glasgow, Scotland, United Kingdom
- ↵∗Reprint requests and correspondence:
Dr. Scott D. Solomon, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02445.
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.
Dr. Packer has served as a consultant for Novartis, Actelion, Sanofi, Cardiokinetix, BioControl, Janssen, Amgen, AMAG, Daiichi, CardioMEMS, AstraZeneca, Cardiorentis, Boehringer Ingelheim, and Cardiorentis. Drs. Zile, Rouleau, Swedberg, Desai, McMurray, and Solomon have served as a consultant for, or received research support from Novartis, sponsor of the PARADIGM-HF trial. Dr. Zile has served as a member of the executive committee for Novartis. Dr. Swedberg has consulted for and received research support from Novartis. Dr. Desai has served as a consultant for St. Jude Medical, Merck, and Relypsa. Drs. Lefkowitz and Shi are employees of Novartis Pharmaceuticals Corporation. Dr. McMurray’s employer, the University of Glasgow, was paid by Novartis for Dr. McMurray’s time spent as cochairman of the PARADIGM-HF trial as well as coprincipal investigator for the PARADIGM-HF, PARAGON-HF, and ATMOSPHERE trials and meetings related to those trials as well as LCZ696 and aliskiren; for some of the aforementioned meetings, he has had his travel and accommodations paid for by Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to report.
- Received September 2, 2015.
- Revision received October 22, 2015.
- Accepted October 31, 2015.
- 2016 American College of Cardiology Foundation