Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial

著者: Derek J. Hausenloy, Rajesh Kharbanda, Ulla Møller, Manish Ramlall, Jens Aarøe, Robert J. Butler, Heerajnarain Bulluck, Tim Clayton, Ali Dana, Matthew Dodd, Thomas Engstrøm, Richard D. Evans, Jens Flensted Lassen, Erika Frischknecht Christensen, José M. García‐Ruiz, Diana A Gorog, Jakob Hjort, Richard F Houghton, Borja Ibáñez, Rosemary Knight, Freddy Lippert, Jacob Thomsen Lønborg, Michael Mæng, Dejan Milasinovic, Ranjit More, Jennifer M. Nicholas, Lisette Okkels Jensen, Alexander Perkins, Nebojša Radovanović, Roby Rakhit, Jan Ravkilde, Alisdair Ryding, Michael Rahbek Schmidt, Ingunn S. Riddervold, Henrik Toft Sørensen, Goran Stanković, Madhusudhan Varma, Ian Webb, Christian Juhl Terkelsen, John P. Greenwood, Derek M. Yellon, Hans Erik Bøtker, Anders Junker, Anne Kaltoft, Morten Madsen, Evald Høj Christiansen, Lars Jakobsen, Steen Carstensen, Steen Dalby Kristensen, Troels Thim, Karin Møller Pedersen, Mette Tidemand Korsgaard, Allan Iversen, Erik Jørgensen, Francis R. Joshi, Frants Pedersen, Hans Henrik Tilsted, Karam Alzuhairi, Kari Saunamäki, Lene Holmvang, Ole Ahlehof, Rikke Sørensen, Steffen Helqvist, B. Màrk, Anton Boel Villadsen, Bent Raungaard, Leif Thuesen, Martin Kirk Christiansen, Philip Freeman, Svend Eggert Jensen, Charlotte Schmidt Skov, Ahmed Aziz, Henrik Steen Hansen, Julia Ellert, Karsten Tange Veien, Knud Erik Pedersen, Knud Hansen, Ole Ahlehoff, Helle Cappelen, Daniel Wittrock, Poul Anders Hansen, Jens Peter Ankersen, Kim Witting Hedegaard, John Kempel, Henning Kaus, Dennis Erntgaard, Danny Mejsner Pedersen, Matthias Giebner, Troels Martin Hansen, Mina Radovanović, Maja Prodanović, Lidija Savić, Marijana Pejic, Dragan Matić, Ana Ušćumlić, Ida Subotić, Ratko Lasica, Vladan Vukcevic, Alfonso Suárez, Beatriz Samaniego, César Morı́s, Eduardo Segovia, Hernandez Ernesto, Íñigo Lozano, Isaac Pascual, José M. Vegas-Valle, José Rozado, Juan Rondán, Pablo Avanzas, Raquel del Valle, Remigio Padrón, Alfonso García-Castro, A. Cubillos Arango, Ana B. Medina-Cameán, Ana I. Fente, Ana Muriel-Velasco, Ángeles Pomar-Amillo, César L. Roza, César M. Martínez-Fernández, Covadonga Buelga-Díaz, David Fernández-Gonzalo, Elena Fernández, Eloy Díaz-González, Eugenio Martinez-González, Fernando Iglesias-Llaca, Fernando M. Viribay, Francisco J. Fernández-Mallo, Francisco J. Hermosa, Ginés Martínez-Bastida, Javier Goitia-Martín, José L. Vega-Fernández, Jose M. Tresguerres, Juan A. Rodil-Díaz, Lara Villar-Fernández, Lucila Alberdi, Luis Abella-Ovalle, Manuel de la Roz, Marcos Fernández-Carral Fernández-Carral, María C. Naves, M.Córdoba Peláez, M. Fuentes, María García-Alonso, María Jesús García Villanueva, María S. Vinagrero, María Vázquez-Suárez, Marta Martínez-Valle, Marta Nonide, Mónica Pozo-López, Pablo Bernardo-Alba, Pablo Galván-Núñez, Polácido J. Martínez-Pérez, Rafael Castro, Raquel Suárez-Coto, Raquel Suárez-Noriega, Rocío Guinea, R Bangueses Quintana, Sara de Cima, Segundo A. Hedrera, Sonia I. Laca, Susana Llorente-Álvarez, Susana Pascual, Teodorna Cimas, Anthony Mathur, Eleanor McFarlane-Henry, Gerry Leonard, Jessry Veerapen, Mark Westwood, Martina Colicchia, Mary Prossora, Mervyn Andiapen, Saidi Mohiddin, Valentina Lenzi, Jun Hua Chong, Rohin Francis, Amy Pine, Caroline Jamieson-Leadbitter, Debbie Neal, Jamilah Din, Jane D. McLeod, Josh Roberts, Karin Poloková, Kristel Longman, L.L. Penney, Nicki Lakeman, Nicki Wells, Oliver Hopper, P Y Coward, Peter O’Kane, Ruth Harkins, Samantha Guyatt, Sarah Kennard, Sarah Orr, Stephanie Horler, Steve Morris, Tom Walvin, Tom Snow, Michael Cunnington, Amanda Burd, Anne Gowing, Arvindra Krishnamurthy, Charlotte Harland, D. R. Norfolk, D Johnstone, Hannah Newman, Helen L. Reed, James P. O’Neill, John P. Greenwood, Josephine Cuxton, Julie H. Corrigan, Kathryn Somers, Michelle A. Anderson, Natalie Burton-Wood, Petra Bijsterveld, Richard Brogan, Tony Ryan, Vivek Kodoth, Arif Khan, Deepa Sebastian, Diana A. Gorog, Georgina Boyle, Lucy Shepherd, Mahmood Hamid, Mohamed Farag, Nicholas Spinthakis, Paulina Waitrak, P. De Sousa, Rishma Bhatti, Victoria Oliver, Sarah Walshe, Toral Odedra, Ying X. Gue, Rahim Kanji, Alisdair Ryding, Amanda Ratcliffe, Angela Merrick, Carol Horwood, Charlotte Sarti, Clint Maart, Donna Moore, Francesca Dockerty, Karen Baucutt, Louise Pitcher, Mary Ilsley, Millie Clarke, Rachel Germon, Sara Costa Gomes, Clare Thomas, Sunil Nair, Jocasta Staines, Susan Nicholson, Oliver Watkinson, Ian Gallagher, Faye Nelthorpe, Janine Musselwhite, Konrad Großer, Leah Stimson, Michelle Eaton, Richard Heppell, Sharon Turney, Victoria Horner, Natasha Schumacher, Angela Moon, Paula Mota, Joshua O'Donnell, Abeesh Panicker, Anntoniette Musa, Luke Tapp, Suresh Krishnamoorthy, Valerie Ansell, Danish Ali, Samantha Hyndman, Prithwish Banerjee, Martin Been, Ailie Mackenzie, Andrew McGregor, David Hildick‐Smith, Felicity Champney, Fiona Ingoldby, Kirstie Keate, Lorraine Bennett, Nicola Skipper, Sally Gregory, Scott Harfield, Alexandra Mudd, Christopher Wragg, David Barmby, Ever Grech, Ian Hall, Janet Middle, Joann Barker, Joyce Fofie, Julian Gunn, Kay Housley, L Cockayne, Louise Weatherlley, Nana Theodorou, Nigel Wheeldon, Pene Fati, Robert F. Storey, J. David Richardson, Javed Iqbal, Zul Adam, Sarah Brett, Michael Agyemang, Cecilia Tawiah, Kai Hogrefe, Prashanth Raju, Christine Braybrook, Jay Gracey, Molly Waldron, Rachael Holloway, Senem Burunsuzoglu, Sian Sidgwick, Simon Hetherington, Charmaine Beirnes, O. Fernández, Nicoleta Lazar, Abigail Knighton, Amrit Rai, Amy Hoare, Ian Webb, Jonathan Breeze, Katherine J. Martin, Michelle Andrews, Sheetal Patale, Amy Bennett, Andrew Smallwood, Elizabeth A. Radford, James Cotton, Joe Martins, Lauren Wallace, Sarah Milgate, Shahzad Munir, Stella Metherell, V Cottam, Ian Massey, Jane Copestick, Jane Delaney, J Wain, Kully Sandhu, Lisa M. Emery, Robert J. Butler, C. Richard Hall, Chiara Bucciarelli‐Ducci, Rissa Besana, Jodie Hussein, Sheila M. Bell, Abby Gill, Emily Bales, Gary Polwarth, Clare East, Ian Smith, Joana Oliveira, Saji Victor, Sarah Woods, Stephen P. Hoole, Angelo Ramos, Annaliza Sevillano, Anne Nicholson, Ashley Solieri, Emily Redman, Jean Byrne, Joan Joyce, Joanne Riches, John R. Davies, Kezia Allen, Louie Saclot, Madelaine Ocampo, Mark Vertue, Natasha Christmas, Raiji Koothoor, Reto Gamma, Wilson Alvares, Stacey Pepper, Barbara Kobson, Christy Reeve, Iqbal Malik, E. Chester, Heidi Saunders, Idah Mojela, Joanna Smee, Justin Davies, Nina Davies, Piers Clifford, Priyanthi Dias, Ramandeep Kaur, Sílvia Moreira, Yousif Ahmad, Lucy Tomlinson, Clare Pengelley, Amanda Bidle, Sharon Spence, Rasha Al‐Lamee, Urmila Phuyal, Hakam Abbass, Tuhina Bose, Rebecca Elliott, Aboo Foundun, Alan Chung, Beth Freestone, Dr Kaeng Lee, Dr Mohamed Elshiekh, George Pulikal, Gurbir Bhatre, James Douglas, Lee Kaeng, Mike Pitt, Richard Watkins, Simrat Gill, Amy Hartley, Andrew Lucking, B. Moreby, Damaris Darby, Ellie Corps, Georgina Parsons, Gianluigi De Mance, Gregor Fahrai, Jennifer Turner, Jeremy P. Langrish, Lisa Gaughran, Mathias Wolyrum, Mohammed Azkhalil, Rachel Bates, Rachel Given, Rajesh Kharbanda, Rebecca Douthwaite, Steph Lloyd, Stephen Neubauer, Deborah Barker, Ali Dana, Anne Suttling, Charlotte Turner, Clare Smith, Colin Longbottom, Ross David, D.R. Cunliffe, Emily R. Cox, Helena Whitehead, Karen Hudson, Leslie N. Jones, Martin Drew, N.S. Chant, Peter Haworth, Robert Capel, Rosalynn Austin, Serena Howe, Trevor Smith, Alex Hobson, Philip C. Strike, H. Griffiths, Brijesh Anantharam, Pearse Jack, Emma Thornton, Adrian B. Hodgson, Alan Jennison, Anna McSkeane, Bethany Smith, Caroline Shaw, Chris Leathers, Elissa Armstrong, Gayle Carruthers, Holly Simpson, Jan D. Smith, Jeremy Hodierne, Julie Kelly, Justin Barclay, Kerry Scott, Lisa Gregson, Louise Buchanan, Louise McCormick, Madhusudhan Varma, Nicci Kelsall, Rachel Mcarthy, R. E. Taylor, Rebecca F. Thompson, Rhidian J. Shelton, Roger K. Moore, Sharon Tomlinson, Sunil Thambi, Theresa Cooper, Trevor Oakes, Zakhira Deen, C Relph, Scott Prentice, Lorna Hall, Angela Dillon, Deborah Meadows, Emma Frank, Helene Markham-Jones, Isobel Thomas, Joanne Gale, Joanne Denman, Joanne Gale, John P. O’Connor, Julia Hindle, Karen Jackson-Lawrence, Karen Warner, Kelvin H. Lee, Robert A. Upton, Ruth Elston, Sandra J. Lee, Vinod Venugopal, Amanda Finch, Catherine Fleming, C Whiteside, Chris Pemberton, Conor Wilkinson, Deepa Sebastian, Ella Riedel, Gaia Giuffrida, Gillian Burnett, Helen Spickett, James Glen, Janette Brown, Lauren Thornborough, L. Pedley, Maureen Morgan, Natalia Waddington, O Brennan, Ranjit More, Rebecca Brady, Stephen Preston, Chris Loder, Ionela Vlad, Julia Laurence, Angelique Smit, Kirsty Dimond, Michelle Hayes, Loveth Paddy, Jacolene Crause, Nadifa Amed, Priya Kaur-Babooa, Roby Rakhit, Tushar Kotecha, Hossam Fayed, Rohin Francis, Antonis N. Pavlidis, Bernard Prendergast, Brian Clapp, Divaka Perara, E. Neely Atkinson, Howard S. Ellis, Karen M. Wilson, Kirsty Gibson, Megan Smith, Muhammed Zeeshan Khawaja, Ruth Sanchez-Vidal, Simon Redwood, Sophie Jones, Aoife Tipping, Anu Mary Oommen, Cara Hendry, DR Fazin Fath-Orboubadi, Hannah Phillips, Laurel Kolakaluri, Martin Sherwood, Sarah Mackie, S Aleti, Thabitha Charles, L Alvarez Roy, R HENDERSON, Rod Stables, Simon Redwood, Michael Marber, Alan Berry, Andrew N. Redington, Kristian Thygesen, Henning Andersen, Colin Berry, Andrew Copas, Tom Meade, Henning Kelbæk, Héctor Bueno, Paul von Weitzel‐Mudersbach, Grethe Andersen, Andrew Ludman, Nick Cruden, Dragan Topic, Zlatko Mehmedbegović, Jesús María de la Hera Galarza, Steve Robertson, Laura Van Dyck, Rebecca Chu, Josenir Astarci, Zahra Jamal, Daniel Hetherington, L Collier - The Lancet 2019 被引用: 324

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.