High-dose influenza vaccine to reduce clinical outcomes in high-risk cardiovascular patients: Rationale and design of the INVESTED trial.

Journal Article (Journal Article;Multicenter Study;Pragmatic Clinical Trial)

BACKGROUND: Influenza leads to significant cardiopulmonary morbidity and mortality-particularly in patients with cardiovascular disease-that may be prevented with a standard influenza vaccine. However, patients with cardiovascular conditions have a reduced immune response to influenza vaccine, potentially resulting in reduced effectiveness for preventing clinical events. High-dose vaccine augments immune response in cardiac patients, suggesting that a high-dose influenza vaccination strategy may further reduce morbidity and mortality. Alternatively, broader coverage with an influenza vaccine containing an increased number of viral strains is an alternative strategy without direct evaluation. RESEARCH DESIGN AND METHODS: INfluenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated heart failure (INVESTED) is a pragmatic, randomized, double-blind, parallel-group, active-controlled trial comparing the effectiveness of an annual vaccination strategy of high-dose trivalent versus standard-dose quadrivalent influenza vaccine in patients with a history of recent heart failure or myocardial infarction hospitalization. The trial will enroll approximately 9,300 patients over 4 influenza seasons. The primary hypothesis is that high-dose influenza vaccine will reduce the composite outcome of all-cause mortality and hospitalization from a cardiovascular or pulmonary cause compared with standard-dose influenza vaccine within each enrolling season. Approximately 1,300 primary outcome events will provide >90% power to detect an 18% relative risk reduction at a 2-sided α level of .05. CONCLUSION: INVESTED is the largest and longest study to assess whether high-dose influenza vaccine is superior to standard-dose influenza vaccine in reducing cardiopulmonary events in a high-risk cardiovascular population (ClinicalTrials.gov Identifier: NCT02787044).

Full Text

Duke Authors

Cited Authors

  • Vardeny, O; Udell, JA; Joseph, J; Farkouh, ME; Hernandez, AF; McGeer, AJ; Talbot, HK; Bhatt, DL; Cannon, CP; Goodman, SG; Anand, I; DeMets, DL; Temte, J; Wittes, J; Nichol, K; Yancy, CW; Gaziano, JM; Cooper, LS; Kim, K; Solomon, SD

Published Date

  • August 2018

Published In

Volume / Issue

  • 202 /

Start / End Page

  • 97 - 103

PubMed ID

  • 29909156

Pubmed Central ID

  • PMC6067954

Electronic International Standard Serial Number (EISSN)

  • 1097-6744

Digital Object Identifier (DOI)

  • 10.1016/j.ahj.2018.05.007


  • eng

Conference Location

  • United States