Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial
Authors: Derek J Hausenloy, Rajesh K Kharbanda, Ulla Kristine Møller, Manish Ramlall, Jens Aarøe, Robert Butler, Heerajnarain Bulluck, Tim Clayton, Ali Dana, Matthew Dodd, Thomas Engstrom, Richard Evans, Jens Flensted Lassen, Erika Frischknecht Christensen, José Manuel Garcia-Ruiz, Diana A Gorog, Jakob Hjort, Richard F Houghton, Borja Ibanez, Rosemary Knight, Freddy K Lippert, Jacob T Lønborg, Michael Maeng, Dejan Milasinovic, Ranjit More, Jennifer M Nicholas, Lisette Okkels Jensen, Alexander Perkins, Nebojsa Radovanovic, Roby D Rakhit, Jan Ravkilde, Alisdair D Ryding, Michael R Schmidt, Ingunn Skogstad Riddervold, Henrik Toft Sørensen, Goran Stankovic, 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 Joshi, Frants Pedersen, Hans Henrik Tilsted, Karam Alzuhairi, Kari Saunamäki, Lene Holmvang, Ole Ahlehof, Rikke Sørensen, Steffen Helqvist, Bettina Løjmand Mark, 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 Veien, Knud Erik Pedersen, Knud Nørregård 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 Hansen, Mina Radosavljevic-Radovanovic, Maja Prodanovic, Lidija Savic, Marijana Pejic, Dragan Matic, Ana Uscumlic, Ida Subotic, Ratko Lasica, Vladan Vukcevic, Alfonso Suárez, Beatriz Samaniego, César Morís, Eduardo Segovia, Ernesto Hernández, Iñigo Lozano, Isaac Pascual, Jose M. Vegas-Valle, José Rozado, Juan Rondán, Pablo Avanzas, Raquel del Valle, Remigio Padrón, Alfonso García-Castro, Amalia 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, Lucía Alberdi, Luis Abella-Ovalle, Manuel de la Roz, Marcos Fernández-Carral Fernández-Carral, María C. Naves, María C. Peláez, María D. Fuentes, María García-Alonso, María J. 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, Rosa B. 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 Chong, Rohin Francis, Amy Pine, Caroline Jamieson-Leadbitter, Debbie Neal, J. Din, Jane McLeod, Josh Roberts, Karin Polokova, Kristel Longman, Lucy Penney, Nicki Lakeman, Nicki Wells, Oliver Hopper, Paul 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, Derek Norfolk, Donna Johnstone, Hannah Newman, Helen Reed, James O'Neill, John Greenwood, Josephine Cuxton, Julie Corrigan, Kathryn Somers, Michelle Anderson, Natalie Burtonwood, Petra Bijsterveld, Richard Brogan, Tony Ryan, Vivek Kodoth, Arif Khan, Deepti Sebastian, Diana Gorog, Georgina Boyle, Lucy Shepherd, Mahmood Hamid, Mohamed Farag, Nicholas Spinthakis, Paulina Waitrak, Phillipa De Sousa, Rishma Bhatti, Victoria Oliver, Siobhan Walshe, Toral Odedra, Ying 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 Gomes, Thomas Clare, 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 Sadasiva 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, Laura Cockayne, Louise Weatherlley, Nana Theodorou, Nigel Wheeldon, Pene Fati, Robert F. Storey, James Richardson, Javid 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, Olga Fernandez, Nicoleta Lazar, Abigail Knighton, Amrit Rai, Amy Hoare, Ian Webb, Jonathan Breeze, Katherine Martin, Michelle Andrews, Sheetal Patale, Amy Bennett, Andrew Smallwood, Elizabeth Radford, James Cotton, Joe Martins, Lauren Wallace, Sarah Milgate, Shahzad Munir, Stella Metherell, Victoria Cottam, Ian Massey, Jane Copestick, Jane Delaney, Jill Wain, Kully Sandhu, Lisa Emery, Robert Butler, Charlotte Hall, Chiara Bucciarelli-Ducci, Rissa Besana, Jodie Hussein, Sheila Bell, Abby Gill, Emily Bales, Gary Polwarth, Clare East, Ian Smith, Joana Oliveira, Saji Victor, Sarah Woods, Stephen Hoole, Angelo Ramos, Annaliza Sevillano, Anne Nicholson, Ashley Solieri, Emily Redman, Jean Byrne, Joan Joyce, Joanne Riches, John 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, Emma Chester, Heidi Saunders, Idah Mojela, Joanna Smee, Justin Davies, Nina Davies, Piers Clifford, Priyanthi Dias, Ramandeep Kaur, Silvia 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, Berni Moreby, Damaris Darby, Ellie Corps, Georgina Parsons, Gianluigi De Mance, Gregor Fahrai, Jenny Turner, Jeremy 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, David Ross, Denise Cunliffe, Emily Cox, Helena Whitehead, Karen Hudson, Leslie Jones, Martin Drew, Nicholas Chant, Peter Haworth, Robert Capel, Rosalynn Austin, Serena Howe, Trevor Smith, Alex Hobson, Philip Strike, Huw Griffiths, Brijesh Anantharam, Pearse Jack, Emma Thornton, Adrian Hodgson, Alan Jennison, Anna McSkeane, Bethany Smith, Caroline Shaw, Chris Leathers, Elissa Armstrong, Gayle Carruthers, Holly Simpson, Jan Smith, Jeremy Hodierne, Julie Kelly, Justin Barclay, Kerry Scott, Lisa Gregson, Louise Buchanan, Louise McCormick, Madhusudhan Varma, Nicci Kelsall, Rachel Mcarthy, Rebecca Taylor, Rebecca Thompson, Rhidian Shelton, Roger Moore, Sharon Tomlinson, Sunil Thambi, Theresa Cooper, Trevor Oakes, Zakhira Deen, Chris Relph, Scott prentice, Lorna Hall, Angela Dillon, Deborah Meadows, Emma Frank, Helene Markham-Jones, Isobel Thomas, Joanne Gale, Joanne Denman, Joanne Gale, John O'Connor, Julia Hindle, Karen Jackson-Lawrence, Karen Warner, Kelvin Lee, Robert Upton, Ruth Elston, Sandra Lee, Vinod Venugopal, Amanda Finch, Catherine Fleming, Charlene Whiteside, Chris Pemberton, Conor Wilkinson, Deepa Sebastian, Ella Riedel, Gaia Giuffrida, Gillian Burnett, Helen Spickett, James Glen, Janette Brown, Lauren Thornborough, Lauren Pedley, Maureen Morgan, Natalia Waddington, Oliver 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 Pavlidis, Bernard Prendergast, Brian Clapp, Divaka Perara, Emma Atkinson, Howard Ellis, Karen Wilson, Kirsty Gibson, Megan Smith, Muhammed Zeeshan Khawaja, Ruth Sanchez-Vidal, Simon Redwood, Sophie Jones, Aoife Tipping, Anu Oommen, Cara Hendry, DR Fazin Fath-Orboubadi, Hannah Phillips, Laurel Kolakaluri, Martin Sherwood, Sarah Mackie, Shilpa Aleti, Thabitha Charles, Liby Roy, Rob Henderson, Rod Stables, Simon Redwood, Michael Marber, Alan Berry, Andrew Redington, Kristian Thygesen, Henning Rud Andersen, Colin Berry, Andrew Copas, Tom Meade, Henning Kelbæk, Hector Bueno, Paul von Weitzel-Mudersbach, Grethe Andersen, Andrew Ludman, Nick Cruden, Dragan Topic, Zlatko Mehmedbegovic, Jesus Maria de la Hera Galarza, Steven Robertson, Laura Van Dyck, Rebecca Chu, Josenir Astarci, Zahra Jamal, Daniel Hetherington, Lucy Collier
Journal: The Lancet (2019)

BackgroundRemote 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.MethodsWe 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.FindingsBetween 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.InterpretationRemote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI.FundingBritish Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.