aCenter for Chronic Disease Outcomes Research, Minneapolis VA Health Care System, and University of Minnesota, Minneapolis, MNbCardiovascular Division, Department of Medicine, Peter Munk Cardiac Centre, Toronto General Hospital and Women's College Hospital, University of Toronto, Toronto, Ontario, CanadacBoston VA Health Care System, and Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MAdCardiovascular Division, Department of Medicine, Peter Munk Cardiac Centre, University of Toronto, Toronto, Ontario, CanadaeCardiology Division, Department of Medicine, Duke University School of Medicine, Durham, NCfDepartment of Microbiology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, CanadagDivision of Infectious Diseases, Department of Medicine, Vanderbilt University, Nashville, TNhBrigham and Women's Hospital Heart & Vascular Center, and Harvard Medical School, Boston, MAiDivision of Cardiology, Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, CanadajSan Diego and Minneapolis VA Health Care Systems and University of Minnesota, San Diego, CA, and Minneapolis, MNkDepartment of Statistics and Biostatistics, University of Wisconsin-Madison, Madison, WIlDepartment of Family Medicine and Community Health, University of Wisconsin-Madison, Madison, WImStatistics Collaborative, Inc., Washington, DCnCardiovascular Division, Northwestern University Feinberg School of Medicine, Chicago, ILoNational Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
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BackgroundInfluenza 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 methodsINfluenza 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.ConclusionINVESTED 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).