Publication Type : Journal Article
Publisher : Elsevier BV
Source : The Lancet
Url : https://doi.org/10.1016/s0140-6736(18)30832-8
Campus : Kochi
School : School of Medicine
Year : 2018
Abstract : Background Myocardial injury after non-cardiac surgery (MINS) increases the risk of cardiovascular events and deaths, which anticoagulation therapy could prevent. Dabigatran prevents perioperative venous thromboembolism, but whether this drug can prevent a broader range of vascular complications in patients with MINS is unknown. The MANAGE trial assessed the potential of dabigatran to prevent major vascular complications among such patients. Methods In this international, randomised, placebo-controlled trial, we recruited patients from 84 hospitals in 19 countries. Eligible patients were aged at least 45 years, had undergone non-cardiac surgery, and were within 35 days of MINS. Patients were randomly assigned (1:1) to receive dabigatran 110 mg orally twice daily or matched placebo for a maximum of 2 years or until termination of the trial and, using a partial 2-by-2 factorial design, patients not taking a proton-pump inhibitor were also randomly assigned (1:1) to omeprazole 20 mg once daily, for which results will be reported elsewhere, or matched placebo to measure its effect on major upper gastrointestinal complications. Research personnel randomised patients through a central 24 h computerised randomisation system using block randomisation, stratified by centre. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary efficacy outcome was the occurrence of a major vascular complication, a composite of vascular mortality and non-fatal myocardial infarction, non-haemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism. The primary safety outcome was a composite of life-threatening, major, and critical organ bleeding. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01661101. Findings Between Jan 10, 2013, and July 17, 2017, we randomly assigned 1754 patients to receive dabigatran (n=877) or placebo (n=877); 556 patients were also randomised in the omeprazole partial factorial component. Study drug was permanently discontinued in 401 (46%) of 877 patients allocated to dabigatran and 380 (43%) of 877 patients allocated to placebo. The composite primary efficacy outcome occurred in fewer patients randomised to dabigatran than placebo (97 [11%] of 877 patients assigned to dabigatran vs 133 [15%] of 877 patients assigned to placebo; hazard ratio [HR] 0·72, 95% CI 0·55–0·93; p=0·0115). The primary safety composite outcome occurred in 29 patients (3%) randomised to dabigatran and 31 patients (4%) randomised to placebo (HR 0·92, 95% CI 0·55–1·53; p=0·76). Interpretation Among patients who had MINS, dabigatran 110 mg twice daily lowered the risk of major vascular complications, with no significant increase in major bleeding. Patients with MINS have a poor prognosis; dabigatran 110 mg twice daily has the potential to help many of the 8 million adults globally who have MINS to reduce their risk of a major vascular complication. Funding Boehringer Ingelheim and Canadian Institutes of Health Research.
Cite this Research Publication : P J Devereaux, Emmanuelle Duceppe, Gordon Guyatt, Vikas Tandon, Reitze Rodseth, Bruce M Biccard, Denis Xavier, Wojciech Szczeklik, Christian S Meyhoff, Jessica Vincent, Maria Grazia Franzosi, Sadeesh K Srinathan, Jason Erb, Patrick Magloire, John Neary, Mangala Rao, Prashant V Rahate, Navneet K Chaudhry, Bongani Mayosi, Miriam de Nadal, Pilar Paniagua Iglesias, Otavio Berwanger, Juan Carlos Villar, Fernando Botto, John W Eikelboom, Daniel I Sessler, Clive Kearon, Shirley Pettit, Mukul Sharma, Stuart J Connolly, Shrikant I Bangdiwala, Purnima Rao-Melacini, Andreas Hoeft, Salim Yusuf, P.J. Devereaux, Emmanuelle Duceppe, Shrikant I. Bangdiwala, Stuart Connolly, John Eikelboom, Gordon Guyatt, Clive Kearon, Shirley Pettit, Janice Pogue, Reitze Rodseth, Daniel I. Sessler, Jessica Vincent, Salim Yusuf, Jessica Vincent, Sara Di Diodato, Zora Gasic, Louise J. Mastrangelo, Sarah H. Molnar, Shirley Pettit, Jennifer L. Swanson, Makayla L. Tosh, Jennifer R. Wells, Fernando Botto, Rafael Diaz, Clara K. Chow, Otavio Berwanger, Beatriz Gonzales, P.J. Devereaux, Vikas Tandon, Juan Carlos Villar, Skarlet Vásquez, Petr Jansky, Radovan Dušek, Christian S. Meyhoff, Pierre Coriat, Andreas Hoeft, Maria Wittmann, Gerald Yonga, Denis Xavier, Mangala Rao, Nandini Mathur, Maria Grazia Franzosi, Elena Seletti, German Malaga, Bernadette A. Tumanan-Mendoza, Maria Pamela A. Tagle, Wojciech Szczeklik, Bruce M. Biccard, Pablo Alonso-Coello, Ekaterine Popova, Martin Shields, Daniel I. Sessler, P.J. Devereaux, Bruce M. Biccard, Stuart Connolly, Emmanuelle Duceppe, John Eikelboom, Gordon Guyatt, Andreas Hoeft, Petr Jansky, Clive Kearon, Yannick Le Manach, Paul Moayyedi, Shirley Pettit, Janice Pogue, Reitze Rodseth, Daniel I. Sessler, Sander van Zanten, Juan Carlos Villar, Jessica Vincent, Salim Yusuf, P.J. Devereaux, Pablo Alonso-Coello, Otavio Berwanger, Bruce M. Biccard, Fernando Botto, Clara K. Chow, Stuart Connolly, Pierre Coriat, Rafael Diaz, Emmanuelle Duceppe, John Eikelboom, Edith Fleischmann, Maria Grazia Franzosi, Amit Garg, Gordon Guyatt, Andreas Hoeft, Petr Jansky, Kamilu Karaye, Clive Kearon, Yannick Le Manach, German Malaga, Edward McFalls, Christian S. Meyhoff, Paul Moayyedi, Shirley Pettit, Janice Pogue, Reitze Rodseth, Daniel I. Sessler, Alben Sigamani, Martin Shields, Wojciech Szczeklik, Bernadette A. Tumanan-Mendoza, Sander van Zanten, Juan Carlos Villar, Jessica Vincent, Denis Xavier, Gerald Yonga, Salim Yusuf, Stuart Connolly, Emilie Belley-Côté, Grzegorz Biedroń, Flavia Borges, Steffan Frosi Stella, Christian Haarmark Nielsen, Darryl P. Leong, Christian S. Meyhoff, Jessica Spence, Allen Tran, Katarzyna Wawrzycka-Adamczyk, Stephen S. Yang, Terence Yung, D. George Wyse, Davy Cheng, David E. Johnstone, George A. Wells, Philip Joseph, Ameen Patel, Darryl P. Leong, Krysten Gregus, Kelly Lawrence, Lindsay Doharris, David Conen, Jason Cheung, Jim Douketis, Douglas Wright, Spencer Wikkerink, William Dechert, Mohamed Panju, Khalid Azzam, Theodore Rapanos, Tomas Van Helder, Anjali Shroff, Jacqueline Hare, Biniam Kidane, Thang Nguyen, Larissa Leydier, Vanessa Bayaraa, Joel Parlow, Deborah A. DuMerton, Amar Thakrar, Jessica Shelley, Benoit Deligne, Roberta Daila Carling, Marko Mrkobrada, George K. Dresser, Michael J. Jacka, Amit Garg, David Hornstein, Gerrit B. Winkelaar, Zoeb Hussain Haider, Pravina Prashant Lanjewar, Valsamma Varughese, Rajneesh Calton, Hemani Ahuja, Preetha George, Ambika Sharma, Keyur Sureshchandra Bhatt, Dhaval Odhavajibhai Mangukiya, Karshan Vira Nandaniya, Viral Vasantrai Parekh, Ashok Bhaskaran Pillai, Vidya P. Menon, Sanjay Channappa Desai, Ravinder Singh Sidhu, Sandeep Kumar Gupta, Robbie K. George, T.R. Gurunath, Leanne W. Drummond, Alexandra M. Torborg, Belinda S. Küsel, Prebashini Naidoo, Datshana P. Naidoo, Chantal Rajah, Zane Farina, Richard Peter von Rahden, Simphiwe Gumede, Chishala Chishala, Ettienne Coetzee, Robert A. Dyer, Johan Diedericks, Piotr Bielański, Bogusz Kaczmarek, Dorota Studzińska, Maciej Zaniewski, Marek Józef Libura, Tomasz Mikołaj Zacharias-Nalichowski, Aurelia A.S. Sega, Jakub Salwa, Mateusz Kózka, Jacek Górka, Anna Wludarczyk, Ilona Nowak-Kózka, Paweł Szczepan Grudzień, Jaroslaw W. Gucwa, Michał Piotr Słowiaczek, Paweł P.D. Dobosz, Ismail Gögenur, Jens Ravn Eriksen, Tine Borup, Tove Kirkegaard, Dan Isbye, Asger Sonne, Lars S. Rasmussen, Sofie Pedersen, Hannibal Troensegaard, Camilla L. Duus, Benedikte M. Halle, Ossian N. Gundel, Katrine F. Bernholm, Kristian Rønsholt Martinsen, Søren Pedersen, Theis S. Itenov, Elena Camio, Carles Vázquez, Silvia Matarin, Esther Cano, Jesús Álvarez-García, Inmaculada India, Aránzazu González-Osuna, Marc Vives, Elena Rosselló, Ana B. Serrano, Maurizio Turiel, Lorenzo Drago, Chiara Colombo, Federica Marra, Lucio Mos, Franco Arteni, Rosalba Lembo, Alessandro Ortalda, Simonetta Passarani, Zhirajr Mokini, Estevao Lanna Figueiredo, Gustavo Fonseca Werner, Joao Luiz Petriz, Lilia Nigro Maia, Ricardo R. Bergo, Dalton Bertolim Precoma, José Francisco Kerr Saraiva, Oscar Gomez Vilamajo, Eduardo Allegrini, Mariano Benzadón, Maria Leonor Parody, Ernesto A. Duronto, Adrián C. Ingaramo, Gustavo Adolfo Parra, Danny Novoa, Scott A. Miller, Sabu Thomas, Sudhakar P. Karlapudi, Mohamad H. Bourji, Subhash Banerjee, Anita Gupta, Isaac O. Opole, Michal Fischer, Petr Jansky, Victor Lecaros Mendoza, Eugenio Borja Reyes, Richard J. Pierson, Martin O. Shields, Clara K. Chow, Pierre Coriat, Vincent Piriou, Maria Wittmann, Kai Zacharowski, Gerald Yonga, Aida Rotta-Rotta, Main Paper, P.J. Devereaux, Emmanuelle Duceppe, Gordon Guyatt, Vikas Tandon, Reitze Rodseth, Bruce M. Biccard, Denis Xavier, Wojciech Szczeklik, Christian S. Meyhoff, Jessica Vincent, Maria Grazia Franzosi, Sadeesh K. Srinathan, Jason Erb, Patrick Magloire, John Neary, Mangala Rao, Prashant Rahate, Navneet Chaudhry, Bogani Mayosi, Miriam de Nadal, Pilar Paniagua Iglesias, Otavio Berwanger, Juan Carlos Villar, Fernando Botto, John Eikelboom, Daniel I. Sessler, Clive Kearon, Shirley Pettit, Mike Sharma, Stuart Connolly, Shrikant I. Bangdiwala, Purnima Rao-Melacini, Andreas Hoeft, Salim Yusuf, Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial, The Lancet, Elsevier BV, 2018, https://doi.org/10.1016/s0140-6736(18)30832-8