High-Dose Versus Standard-Dose Influenza Vaccine and Cardiovascular Outcomes in Older Adults: The FLUNITY-HD Prespecified Pooled Analysis
Abstract
BACKGROUND: The high-dose inactivated influenza vaccine (HD-IIV) has demonstrated superior protection against a range of hospitalization end points versus standard-dose inactivated influenza vaccine (SD-IIV), but its effectiveness against specific cardiovascular outcomes and in those with pre-existing cardiovascular disease (CVD) is not well elucidated. METHODS: In a prespecified secondary analysis of the FLUNITY-HD (Pooled Analysis of Methodologically Harmonized Pragmatic Randomized Trials of High-Dose vs. Standard-Dose Influenza Vaccine Against Severe Clinical Outcomes) individual-level pooled data set integrating 2 methodologically harmonized pragmatic, individually randomized trials conducted in Denmark and Spain, we investigated the relative vaccine effectiveness of HD-IIV versus SD-IIV against severe cardiovascular outcomes and according to pre-existing CVD among adults ≥65 years of age. Data were primarily obtained from routine health care databases, with follow-up from 14 days after vaccination to May 31 the following year. RESULTS: The pooled data set encompassed 466 320 individually randomized participants, of whom 107 700 (23.1%) had a history of CVD. HD-IIV reduced the incidence of hospitalization for influenza or pneumonia, cardiorespiratory disease, laboratory-confirmed influenza, and any cause compared with SD-IIV, irrespective of the presence or absence of pre-existing CVD ( P interaction >0.66 for all outcomes). Compared with the SD-IIV group, the HD-IIV group had a significantly lower incidence of hospitalization for any CVD (HD-IIV, 1.15%, versus SD-IIV, 1.24%; relative vaccine effectiveness, 6.6% [95% CI, 1.6–11.4]; P =0.010), hospitalization for any respiratory disease (HD-IIV, 0.92%, versus SD-IIV, 0.98%; relative vaccine effectiveness, 6.5% [95% CI, 0.7–11.9]; P =0.027), and hospitalization for heart failure (HD-IIV, 0.11%, versus SD-IIV, 0.15%; relative vaccine effectiveness, 21.3% [95% CI, 7.6–33.0]; P =0.003). CONCLUSIONS: In a prespecified pooled analysis of 466 320 individually randomized older adults, HD-IIV reduced the incidence of a wide range of severe cardiovascular and respiratory outcomes compared with SD-IIV, with consistent findings regardless of previous history of CVD. Among cardiovascular outcomes, the protective effect of HD-IIV versus SD-IIV was particularly pronounced against hospitalization for heart failure. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06506812.
Article Details
Authors (333)
Niklas Dyrby Johansen
Department of Cardiology, Copenhagen University Hospital, Herlev and Gentofte, Copenhagen
Daniel Modin
Department of Cardiology, Copenhagen University Hospital, Herlev and Gentofte, Copenhagen
Matthew M. Loiacono
Sanofi, Morristown, NJ
Rebecca C. Harris
Sanofi, Singapore
Marine Dufournet
Sanofi, Lyon, France
Robertus van Aalst
Ayman Chit
Sanofi, Morristown, NJ (M.M.L., R.v.A., A.C.).
Carsten Schade Larsen
Department of Clinical Medicine–Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
Lykke Larsen
Research Unit for Infectious Diseases, Odense University Hospital, Odense, Denmark
Lothar Wiese
Department of Infectious Diseases, Zealand University Hospital, Roskilde, Denmark
Michael Dalager-Pedersen
Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
Brian L. Claggett
Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston
Kira Hyldekær Janstrup
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Carmen Durán-Parrondo
Dirección Xeral de Saúde Pública, Consellería de Sanidade, Xunta de Galicia, Santiago de Compostela, Spain
Marta Piñeiro-Sotelo
Dirección Xeral de Saúde Pública, Consellería de Sanidade, Xunta de Galicia, Santiago de Compostela, Spain
Martín Cribeiro-González
Dirección Xeral de Recursos Económicos, SERGAS, Xunta de Galicia, Santiago de Compostela, Spain
Mónica Conde-Pájaro
Dirección Xeral de Saúde Pública, Consellería de Sanidade, Xunta de Galicia, Santiago de Compostela, Spain
Susana Mirás-Carballal
Dirección Xeral de Saúde Pública, Consellería de Sanidade, Xunta de Galicia, Santiago de Compostela, Spain
Juan-Manuel González-Pérez
Subdirección de Sistemas y Tecnologías de la Información, Consellería de Sanidade, Xunta de Galicia, Santiago de Compostela, Spain
Scott D. Solomon
Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston
Pradeesh Sivapalan
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen
Cyril Jean-Marie Martel
Statens Serum Institut, Copenhagen
Jens Ulrik Stæhr Jensen
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen
Tor Biering-Sørensen
Department of Cardiology, Copenhagen University Hospital, Herlev and Gentofte, Copenhagen
Katja Vu Bartholdy
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Katrine Feldballe Bernholm
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Julie Inge-Marie Helene Borchsenius
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Filip Soeskov Davidovski
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Lise Witten Davodian
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Maria Dons
Department of Cardiology, Copenhagen University Hospital, Herlev and Gentofte, Copenhagen
Lisa Steen Duus
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Caroline Espersen
Department of Cardiology, Copenhagen University Hospital, Herlev and Gentofte, Copenhagen
Frederik Holme Fussing
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Anne Marie Reimer Jensen
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Nino Emanuel Landler
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Adam Cadovius Femerling Langhoff
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Mats Christian Højbjerg Lassen
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Anne Bjerg Nielsen
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Camilla Ikast Ottosen
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Morten Sengeløv
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Kristoffer Grundtvig Skaarup
Department of Cardiology, Copenhagen University Hospital — Herlev and Gentofte, Copenhagen
Ana Maria Abal Senin
Pilar Alonso Vence
Rosa María Álvarez Gil
Talia Alvarez Suarez
Lidia Alvarez Dapia
Jose Manuel Alvarez Pena
Silvia Amoedo Casqueiro
Patricia Aran Abelenda
Josefa Araujo Rodriguez
Ana Ares Martinez
Maria Asensio Nieto
Noelia Belen Ayllon Morcillo
Mónica Barral Carregal
Maria Begoña Baquero Sabajanes
Alejandro Baña Tomé
Lorena Bayon Diz
Damian Bernardez Sende
Beatriz Blanco Salgado
Lucia Bruquet Costa
Faustino Caballero Muinelo
Noelia Cabeiras Alvarez
Maria Guadalupe Cainzos Fernandez
Alba Campero Ojea
Isabel Campos Pardo
Diego Canedo Cotelo
Lidia Carreira Diaz
Miguel Angel Carreiro Alonso
Almudena Carro Orgeira
Adriana Maria Castelo Triñanes
Ana Belen Castelo Vazquez
César Castro Pita
Andrea Castro Sande
Manuel Castro Guizan
Mercedes Castro Bacariza
Maria Jose Castro Castro
Maria Jose Castroman Souto
Sabela Ceide Fernandez
Olga María Ces Ozores
Rebeca Chouza Alonso
Verónica Civeira Pérez
Carla Alexandra Correia Parauta
Ana Isabel Corbal Obelleiro
Angela Coutado Belon
Xurxo Couto Catoira
Ana Isabel Couto Tobío
Evaristo Cuerdo Coton
Angeles Cuiña Caneda
Sonia De Miguel Cañas
Paola De Castro Garcia
Maria Eugenia De Jesús Torrealba Valente
Carmen Del Ojo Paez
María Begoña Del Oro Saez
Romina Deus Suarez
Paula Diaz Lopez
Lucia Diaz Gonzalez
Alejandro Docal Pombo
Marta Dominguez Lago
Beatriz Dominguez Picos
Rita Dominguez Gonzalez
Eva Maria Dominguez Martis
Maria Eulalia Dominguez Vilas
Ángeles Dono Díaz
Olalla Duro Liñares
Olalla Díaz Zuaza
Eloy Díez Polo
Estefania Esmoris Suarez
Rocio Estepa Diaz
Maria Montserrat Estevez Fernandez
Gemma Fandiño Guardado
Veronica Fernandez Gronewold
Noemi Fernandez Martinez
Alfonso Fernandez Vazquez
Susana Fernandez Perez
Raquel Fernandez Rodriguez
Nedea Fernandez Rama
Natalia Fernandez Novelle
Sebastian Estebo Fernández De Las Heras
Marta Fernandez Del Rio
Cristina Fernandez Costa
Anselmo Fernandez Alonso
Monica Beatriz Fernandez Martin
Maria Pilar Fernandez Varela
Rosa Maria Ferro Castaño
Andrea Filgueira Vazquez
Melania Fraga Deus
Milagros Valeria Franco Soñora
Mercedes Fuentes Fernandez
Margarita Galdo Sierra
Verónica Garcia Romero
Carmen Garcia Garcia
Cecilia García Duran
Maria Gestoso Filloy
Maria De La Cruz Gil Rodriguez
Laura Giraldez Groba
Dorotea Gomez Fernandez
Cristina Gomez Lendoiro
Cristina Gomez Lopez
Alejandro Gomez Moldes
Miguel Gonzalez Moron
Laura Gonzalez Carballo
Natalia González Cacho
Maria Gonzalez Fondado
Ana González Isorna
Maria Mar Gonzalez Mendez
Maria Carmen Gonzalez Nisarre
Marina Gonzalez Zar
Cristian Guerreiro Seijas
M.ª del Carmen Guerra Calvelo
Maria Angeles Guzman Ruiz
Maria Luisa Hermida Sanchez
Aida Hermida Trujillo
Maria Belén Hernández González
Laura Iglesias Carballo
Nuria Iglesias Canedo
Rita Iglesias Estevez
Maria Insua Lago
Lorena Íñiguez Tejo
Sara Jacobo Vazquez
Antia Jarazo Miras
Ana Jurjo Costa
Rosa Mª Lage Fontarigo
María Isabel Liñeira Mourón
Maria Del Cielo Lista Rodriguez
Fernando Lois Vidal
Amaya Lois Lama
Carmen Lopez Bolaño
Luz Maria Lopez Castro
Rosa Maria Lopez Cordero
Maria Begoña Lopez Garcia
Rocio Lopez Lopez
Miguel Lopez Potes
Laura Lopez Rodriguez
Ana Lorenzo Olmo
Lucia Lorenzo Quintans
Luis Enrique Lorenzo Vila
Paula Losada Del Rio
Sabela Losada Dieguez
Syra Maceira Guisamonde
Andrea Mallon Gonzalez
Gemma M.ª Marquina Diaz
Ana Maria Millan Agrasar
Nuria Martinez Blanco
Ángela Martinez Martinez
Estrella Martínez Moreira
Olga Martínez Regueira
Karin Meier Cacharo
Diego Mella Tembrás
Raquel Mera Amoedo
Maria Pilar Mera Rodríguez
Fernando Mercador Mouce
Cristina Miguez Torres
Rosa Ana Montaña Rodriguez
Carla Maria Morales Soliño
Jimena Moreira Barros
Maria Concepcion Morigosa Galiano
Iria Mosquera Flores
Mar Mosteiro Valiño
Maria Muiña Rico
Maider Muiños Blanco
Victoria Nartallo Penas
Ursula Nieto Camaño
Teresa Noguerol Gonzalez
Sabela Noval Couceiro
Ana Noya Gonzalez
Maria Elisa Nuñez Losada
Juan Ocon Casal
Pilar Osende Barallobre
María Teresa Otero Barros
Iria Otero Tenorio
Irene Otero Lopez
Veronica Oubiña Cousido
Jesus Padilla Castillo
Rosa Maria Padin Gonzalez
Eva Padrón Lloves
Aurora Pan Regueira
Silvia Parada Gañete
Maria José Parrado Alonso
Mercedes Pedreira Dominguez
Sandra Maria Pedreira Perez
Maria Del Carmen Pereiro Belay
Ana Perez Godas
Carmen Perez Lourido
Maria Perez Neira
Eva Maria Perez Pena
Lara Perez Rodriguez
Nerea Perez Salgado
Ines Perez Sabin
Marta Piedra Viqueira
Dora Pintos Rodriguez
Carmen Portela Sanmartin
Maria Beatriz Prego Garcia
Adrian Prego Del Rio
Ángela Pérez Vazquez
Félix Pérez Herráiz
Olaia Pérez Martínez
Iva Vanusa Pires Reis
Diego Rama Cordeiro
Andrea Raposo Varela
Alejandro Redondo Gerpe
Sonia Regueiro Amoedo
Jose Luis Rey Fole
Fátima Rey Trigo
Thania Rey Villamea
Barbara Rial Seijas
Pablo Robledo Casado
Gemma Rodriguez Alvarez
Carmen Rodriguez Calvo
Susana Rodriguez Carballo
Celia Rodriguez Estoquera
Diana Rodriguez Loureiro
Antonio Rodriguez Pena
Digna Rodriguez Romar
Iria Rodriguez Romar
Alberto Rodriguez Seoane
Cesar Rodriguez Serrada
Susana Rodriguez Simon
Ana Isabel Romero Pintos
Olaya Rosende Pernas
Alejandra Roura Gomez
Adrian Rubio Montalban
Alberto Salmonte Rodriguez
Alba Sanchez Casas
Maria Isolina Santiago Perez
Maria Begoña Santos Padin
Jessica Seco Franco
Victoria Senlle Costas
Melina Soengas Gonzalez
Susana Soliño Lourido
Laura Somoza Copa
Begoña Soriano Lorente
Maria José Soriano Ureña
Norma Suarez Castro
Nuria Suárez Gaiche
Pablo Taboada Pampin
Thiago Taffarel Rios Salazar
Susana Tojo Ramos
Marta Tome Gonzalez
Patricia Torres Álvarez
Angelica Trillo Trillo
Susana Uriz Prado
Luis Angel Varela Nuñez
Cristina Varga Martin
Jacobo Vazquez Marquez
Brais Vazquez Lamazares
Natalia Vazquez Iglesias
Andres Miguel Vazquez Bendaña
Vanesa Vazquez Modia
Begoña Vidal Maroño
Fatima Viñas Castro
Karina Vilas Cabeza
Maria Villoch Garcia
Cristian Vispo Lopez
Xavier Bello Paderne
Miriam Ben García
Alba Camino Mera
Sandra Carnota Antonio
Silvia Cerqueiro Rey
Ana Cotovad Bellas
María José Currás Tuala
Ana Dacosta Urbieta
Isabel Ferreiros Vidal
Iago Giné Vázquez
Alberto Gómez Carballa
Jose Gómez Rial
Montserrat López Franco
Narmeen Mallah
Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
Ángela Manzanares Casteleiro
Lara Martínez Martínez
Federico Martinón-Torres
Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
Esther Montero Campos
Julian Montoto Louzao
Belén Mosquera Pérez
Andres Muy Pérez
Laura Navarro Ramón
Paula Otero Riveira
Jacobo Pardo-Seco
Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
Ana María Pastoriza Mourelle
Sara Pischedda
Josefina Razzini
Lorenzo Redondo Collazo
Patricia Regueiro Casuso
Susana Rey García
Sara Rey Vázquez
Irene Rivero Calle
Carmen Rodríguez-Tenreiro-Sánchez
Genetics, Vaccines, and Infectious Diseases Research Group (GENVIP), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
Ana M.ª Senín Ferreiro
Sonia Serén Fernández
Miriam Taboada Puga
Raquel Vidal Barreiro
María Soledad Vilas Iglesias
Sandra Viz Lasheras
Ouhao Zhu Huang