Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

Bradbury et al., JAMA, doi:10.1001/jama.2022.2910, REMAP-CAP, NCT02735707

Mar 2022

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RCT 1,557 critical patients, showing significantly lower mortality with aspirin, with 97.5% posterior probability of efficacy.

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risk of death, 16.0% lower, HR 0.84, p = 0.05, treatment 165 of 563 (29.3%), control 170 of 521 (32.6%), NNT 30, inverted to make HR<1 favor treatment, Kaplan–Meier, day 90.

risk of no hospital discharge, 16.9% lower, RR 0.83, p = 0.08, treatment 161 of 563 (28.6%), control 167 of 521 (32.1%), NNT 29, adjusted per study, inverted to make RR<1 favor treatment, odds ratio converted to relative risk.

risk of progression, 21.0% lower, RR 0.79, p = 0.02, treatment 204 of 563 (36.2%), control 212 of 521 (40.7%), adjusted per study, odds ratio converted to relative risk, combined death/thrombosis.

risk of progression, 4.8% lower, OR 0.95, p = 0.67, treatment 563, control 521, adjusted per study, inverted to make OR<1 favor treatment, support-free days, primary outcome, RR approximated with OR.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Bradbury et al., 22 Mar 2022, Randomized Controlled Trial, multiple countries, peer-reviewed, 73 authors, study period 30 October, 2020 - 23 June, 2021, trial NCT02735707 (history) (REMAP-CAP).

This Paper Aspirin All

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

Simin Florescu, Delia Stanciu, Mihaela Zaharia, Alma kosa, Daniel Codreanu, Aneela Kidwai, Sobia Masood, Callum Kaye, Amanda Coutts, Lynn Mackay, Charlotte Summers, Petra Polgarova, Neda Farahi, Eleonore Fox, Stephen Mcwilliam, Daniel Hawcutt, Laura Rad, Laura O’malley, Jennifer Whitbread, Dawn Jones, Rachael Dore, Paula Saunderson, Olivia Kelsall, Nicholas Cowley, Laura Wild, Jessica Thrush, Hannah Wood, Karen Austin, János Bélteczki, István Magyar, Ágnes Fazekas, Sándor Kovács, Viktória Szőke, Adrian Donnelly, Martin Kelly, Naoise Smyth, Sinéad O’kane, Declan Mcclintock, Majella Warnock, Ryan Campbell, Edmund Mccallion, Amine azaiz, Cyril Charron, Mathieu Godement, Guillaume Geri, Antoine Vieillard-Baron, Paul Johnson, Shirley Mckenna, Joanne Hanley, Andrew Currie, Barbara Allen, Clare Mcgoldrick, Moyra Mcmaster, Ashwin Mani, Meghena Mathew, Revathi Kandeepan, C Vignesh, Bharath Tv, N Ramakrishnan, Augustian James, Evangeline Elvira, Devachandran Jayakumar, Ramachandran Pratheema, Suresh Babu, R Ebenezer, S Krishnaoorthy, Lakshmi Ranganathan, Manisha Ganesan, Madhu Shree, Eileen Guilder, Magdalena Butler, Keri-Anne Cowdrey, Melissa Robertson, Farisha Ali, Ellie Mcmahon, Eamon Duffy, Yan Chen, Catherine Simmonds, Rachael Mcconnochie, Caroline O’connor, Khaled El-Khawas, Angus Richardson, Dianne Hill, Robert Commons, Hussam Abdelkharim, Rajeev Jha, Michael Kalogirou, Christine Ellis, Vinodh Krishnamurthy, Aibhilin O’connor, Saranya Thurairatnam, Dipak Mukherjee, Agilan Kaliappan, Mark Vertue, Anne Nicholson, Joanne Riches, Gracie Maloney, Lauren Kittridge, Amanda Solesbury, Angelo Ramos, Daniel Collins, Kathy Brickell, Liadain Reid, Michelle Smyth, Patrick Breen, Sandra Spain, Gerard Curley, Natalie Mcevoy, Pierce Geoghegan, Jennifer Clarke, Jon Silversides, Peter Mcguigan, Kathryn Ward, Aisling O’neill, Stephanie Finn, Chris Wright, Jackie Green, Érin Collins, Cameron Knott, Julie Smith, Catherine Boschert, Kitty Slieker, Esther Ewalds, Arnate Sanders, Wendy Wittenberg, Heidi Geurts, Brenda Reeve, William Dechert, Barbara Phillips, Laura Oritz-Ruiz De gordoa, Julia Affleck, Yogesh Apte, Umesh Subbanna, Roland Bartholdy, Thuy Frakking, Jez Pinnell, Matt Robinson, Lisa Gledhill, Tracy Wood, Karuna Keat, Deepak Bhonagiri, Ritesh Sanghavi, Jodie Nema, Megan Ford, Harshel Parikh, Bronwyn Avard, Mary Nourse, Oscar Hoiting, Marco Peters, Els Rengers, Mirjam Evers, Anton Prinssen, Matt Morgan, Jade Cole, Helen Hill, Michelle Davies, Angharad Williams, Emma Thomas, Rhys Davies, Matt Wise, Patrick Grimm, Jens Soukup, Richard Wetzold, Madlen Löbel, Lisa Starke, Francois Lellouche, Patricia Lizotte, Pierre Declerq, Marchalot Antoine, Gelinotte Stephanie, Eraldi Jean-Pierre, Bourgerol François, Beuzelin Marion, Rigaud Philippe, Franck Pourcine, Mehran Monchi, David Luis, Romain Mercier, Anne Sagnier, Nathalie Verrier, Cecile Caplin, Jack Richecoeu, Daniele Combaux, Shidasp Siami, Christelle Aparicio, Sarah Vautier, Asma Jeblaoui, Delphine Lemaire-Brunel, Frédérick Carbonneau, Julie Leblond, Gaetan Plantefeve, Cécile Leparco, Damien Contou, Muriel Fartoukh, Laura Courtin, Vincent Labbe, Guillaume Voiriot, Sara Salhi, Michaël Chassé, François Carrier, Dounia Boumahni, Fatna Benettaib, Ali Ghamraoui, Arnaud Sement, Alexandre Gachet, Alexis Hanisch, Abdelmagid Haffiane, Anne-Hélène Boivin, Amelie Barreau, Elodie Guerineau, Séverine Poupblanc, Pierre Egreteau, Montaine Lefevre, Simon Bocher, Guillaume Le Loup, Lenaïg Le Guen, Vanessa Carn, Melanie Bertel, David Antcliffe, Maie Templeton, Roceld Rojo, Phoebe Coghlan, Joanna Smee, Gareth Barker, André Finn, Gabriele Kreß, Uwe Hoff, Carl Hinrichs, Jens Nee, Euan Mackay, Jon Cort, Amanda Whileman, Thomas Spencer, Nick Spittle, Sarah Beavis, Anand Padmakumar, Katie Dale, Joanne Hawes, Emma Moakes, Rachel Gascoyne, Kelly Pritchard, Lesley Stevenson, Justin Cooke, Karolina Nemeth-Roszpopa, Basanta Gauli, Sirjana Bastola, Grégoire Muller, Mai-Anh Nay, Toufik Kamel, Dalila Benzekri

JAMA, doi:10.1001/jama.2022.2910

IMPORTANCE The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. OBJECTIVE To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). INTERVENTIONS Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. MAIN OUTCOMES AND MEASURES The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from −1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. RESULTS The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, −1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, −0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase,..

Role of the Funder/Sponsor: The study funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The platform trial has 4 regional nonprofit sponsors: Monash University, Melbourne, Victoria, Australia (Australasian sponsor); Utrecht Medical Center, Utrecht, the Netherlands (European sponsor); St Michael's Hospital, Toronto, Ontario, Canada (Canadian sponsor); and the Global Coalition for Adaptive Research, San Francisco, California (US sponsor). Several authors are employees of these organizations. However, beyond the declared author contributions, the sponsors had no additional role. Disclaimer: The views expressed in this publication are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. Dr Seymour is Associate Editor of JAMA, Dr Angus is Senior Editor of JAMA, and Dr Lewis is Statistical Editor of JAMA, but none were involved in any of the decisions regarding review of the manuscript or its acceptance. Group Information: The REMAP-CAP Investigators are listed in Supplement 3. Data Sharing Statement: See Supplement 4. Meeting Presentation: This study was presented at the International Symposium on Intensive Care and Emergency Medicine (ISICEM); March 22, 2022; Brussels, Belgium. Additional Contributions: We are..

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'given': 'Lindsay R.', 'family': 'Berry', 'sequence': 'additional', 'affiliation': [{'name': 'Berry Consultants, Austin, Texas'}]}, { 'given': 'Elizabeth', 'family': 'Lorenzi', 'sequence': 'additional', 'affiliation': [{'name': 'Berry Consultants, Austin, Texas'}]}, { 'given': 'Ryan', 'family': 'Zarychanski', 'sequence': 'additional', 'affiliation': [{'name': 'University of Manitoba, Winnipeg, Canada'}]}, { 'given': 'Yaseen M.', 'family': 'Arabi', 'sequence': 'additional', 'affiliation': [ { 'name': 'King Saud bin Abdulaziz University for Health Sciences and King ' 'Abdullah International Medical Research Center, Riyadh, Saudi ' 'Arabia'}]}, { 'given': 'Djillali', 'family': 'Annane', 'sequence': 'additional', 'affiliation': [ { 'name': 'Hospital Raymond Poincaré (Assistance Publique Hôpitaux de ' 'Paris), Garches, France'}, { 'name': 'Université Versailles SQY–Université Paris Saclay, ' 'Montigny-le-Bretonneux, France'}]}, { 'given': 'Abi', 'family': 'Beane', 'sequence': 'additional', 'affiliation': [{'name': 'University of Oxford, Oxford, England'}]}, { 'given': 'Wilma', 'family': 'van Bentum-Puijk', 'sequence': 'additional', 'affiliation': [{'name': 'University Medical Center Utrecht, Utrecht, the Netherlands'}]}, { 'given': 'Zahra', 'family': 'Bhimani', 'sequence': 'additional', 'affiliation': [{'name': 'St Michael’s Hospital Unity Health, Toronto, Ontario, Canada'}]}, { 'given': 'Shailesh', 'family': 'Bihari', 'sequence': 'additional', 'affiliation': [{'name': 'Flinders University, Bedford Park, South Australia, Australia'}]}, { 'given': 'Marc J. M.', 'family': 'Bonten', 'sequence': 'additional', 'affiliation': [{'name': 'University Medical Center Utrecht, Utrecht, the Netherlands'}]}, { 'given': 'Frank M.', 'family': 'Brunkhorst', 'sequence': 'additional', 'affiliation': [{'name': 'Jena University Hospital, Jena, Germany'}]}, { 'given': 'Adrian', 'family': 'Buzgau', 'sequence': 'additional', 'affiliation': [{'name': 'Monash University, Melbourne, Victoria, Australia'}]}, { 'given': 'Meredith', 'family': 'Buxton', 'sequence': 'additional', 'affiliation': [{'name': 'Global Coalition for Adaptive Research, Los Angeles, California'}]}, { 'given': 'Marc', 'family': 'Carrier', 'sequence': 'additional', 'affiliation': [ {'name': 'Ottawa Hospital Research Institute, Ottawa, Ontario, Canada'}, {'name': 'Institut du Savoir Montfort, Ottawa, Ontario, Canada'}]}, { 'given': 'Allen C.', 'family': 'Cheng', 'sequence': 'additional', 'affiliation': [ {'name': 'Monash University, Melbourne, Victoria, Australia'}, {'name': 'Alfred Health, Melbourne, Victoria, Australia'}]}, { 'given': 'Matthew', 'family': 'Cove', 'sequence': 'additional', 'affiliation': [ { 'name': 'Yong Loo Lin School of Medicine, National University of ' 'Singapore, Singapore'}]}, { 'given': 'Michelle A.', 'family': 'Detry', 'sequence': 'additional', 'affiliation': [{'name': 'Berry Consultants, Austin, Texas'}]}, { 'given': 'Lise J.', 'family': 'Estcourt', 'sequence': 'additional', 'affiliation': [{'name': 'NHS Blood and Transplant, Oxford, England'}]}, { 'given': 'Mark', 'family': 'Fitzgerald', 'sequence': 'additional', 'affiliation': [{'name': 'Berry Consultants, Austin, Texas'}]}, { 'given': 'Timothy D.', 'family': 'Girard', 'sequence': 'additional', 'affiliation': [{'name': 'University of Pittsburgh, Pittsburgh, Pennsylvania'}]}, { 'given': 'Ewan C.', 'family': 'Goligher', 'sequence': 'additional', 'affiliation': [ { 'name': 'Peter Munk Cardiac Centre at University Health Network, Toronto, ' 'Ontario, Canada'}, {'name': 'University of Toronto, Toronto, Ontario, Canada'}]}, { 'given': 'Herman', 'family': 'Goossens', 'sequence': 'additional', 'affiliation': [{'name': 'University of Antwerp, Wilrijk, Belgium'}]}, { 'given': 'Rashan', 'family': 'Haniffa', 'sequence': 'additional', 'affiliation': [ {'name': 'University of Oxford, Bangkok, Thailand'}, { 'name': 'National Intensive Care Surveillance (NICST), Colombo, Sri ' 'Lanka'}]}, { 'given': 'Thomas', 'family': 'Hills', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research Institute of New Zealand (MRINZ), Wellington, ' 'New Zealand'}]}, { 'given': 'David T.', 'family': 'Huang', 'sequence': 'additional', 'affiliation': [{'name': 'University of Pittsburgh, Pittsburgh, Pennsylvania'}]}, { 'given': 'Christopher M.', 'family': 'Horvat', 'sequence': 'additional', 'affiliation': [ { 'name': 'UPMC Children’s Hospital of Pittsburgh, Pittsburgh, ' 'Pennsylvania'}]}, { 'given': 'Beverley J.', 'family': 'Hunt', 'sequence': 'additional', 'affiliation': [{'name': 'Kings Healthcare Partners, London, England'}]}, { 'given': 'Nao', 'family': 'Ichihara', 'sequence': 'additional', 'affiliation': [{'name': 'The University of Tokyo, Tokyo, Japan'}]}, { 'given': 'Francois', 'family': 'Lamontagne', 'sequence': 'additional', 'affiliation': [{'name': 'Université de Sherbrooke, Sherbrooke, Québec, Canada'}]}, { 'given': 'Helen L.', 'family': 'Leavis', 'sequence': 'additional', 'affiliation': [{'name': 'University Medical Center Utrecht, Utrecht, the Netherlands'}]}, { 'given': 'Kelsey M.', 'family': 'Linstrum', 'sequence': 'additional', 'affiliation': [{'name': 'University of Pittsburgh, Pittsburgh, Pennsylvania'}]}, { 'given': 'Edward', 'family': 'Litton', 'sequence': 'additional', 'affiliation': [ {'name': 'Fiona Stanley Hospital, Perth, Western Australia, Australia'}, {'name': 'University of Western Australia, Perth, Australia'}]}, { 'given': 'John C.', 'family': 'Marshall', 'sequence': 'additional', 'affiliation': [{'name': 'St Michael’s Hospital Unity Health, Toronto, Ontario, Canada'}]}, { 'given': 'Daniel F.', 'family': 'McAuley', 'sequence': 'additional', 'affiliation': [ {'name': 'Queen’s University Belfast, Belfast, Northern Ireland'}, {'name': 'Royal Victoria Hospital, Belfast, Northern Ireland'}]}, { 'given': 'Anna', 'family': 'McGlothlin', 'sequence': 'additional', 'affiliation': [{'name': 'Berry Consultants, Austin, Texas'}]}, { 'given': 'Shay P.', 'family': 'McGuinness', 'sequence': 'additional', 'affiliation': [ {'name': 'Monash University, Melbourne, Victoria, Australia'}, {'name': 'Auckland City Hospital, Auckland, New Zealand'}]}, { 'given': 'Saskia', 'family': 'Middeldorp', 'sequence': 'additional', 'affiliation': [{'name': 'Radboud University Medical Center, Nijmegen, the Netherlands'}]}, { 'given': 'Stephanie K.', 'family': 'Montgomery', 'sequence': 'additional', 'affiliation': [{'name': 'University of Pittsburgh, Pittsburgh, Pennsylvania'}]}, { 'given': 'Susan C.', 'family': 'Morpeth', 'sequence': 'additional', 'affiliation': [{'name': 'Middlemore Hospital, Auckland, New Zealand'}]}, { 'given': 'Srinivas', 'family': 'Murthy', 'sequence': 'additional', 'affiliation': [{'name': 'University of British Columbia, Vancouver, Canada'}]}, { 'given': 'Matthew D.', 'family': 'Neal', 'sequence': 'additional', 'affiliation': [{'name': 'University of Pittsburgh, Pittsburgh, Pennsylvania'}]}, { 'given': 'Alistair D.', 'family': 'Nichol', 'sequence': 'additional', 'affiliation': [ {'name': 'Monash University, Melbourne, Victoria, Australia'}, {'name': 'University College Dublin, Dublin, Ireland'}]}, { 'given': 'Rachael L.', 'family': 'Parke', 'sequence': 'additional', 'affiliation': [ {'name': 'Auckland City Hospital, Auckland, New Zealand'}, {'name': 'University of Auckland, Auckland, New Zealand'}]}, { 'given': 'Jane C.', 'family': 'Parker', 'sequence': 'additional', 'affiliation': [{'name': 'Monash University, Melbourne, Victoria, Australia'}]}, { 'given': 'Luis F.', 'family': 'Reyes', 'sequence': 'additional', 'affiliation': [ {'name': 'Universidad de La Sabana, Chia, Colombia'}, {'name': 'Clinica Universidad de La Sabana, Chia, Colombia'}]}, { 'given': 'Hiroki', 'family': 'Saito', 'sequence': 'additional', 'affiliation': [ { 'name': 'St Marianna University School of Medicine, Yokohama City Seibu ' 'Hospital, Yokohama, Japan'}]}, { 'given': 'Marlene S.', 'family': 'Santos', 'sequence': 'additional', 'affiliation': [{'name': 'St Michael’s Hospital Unity Health, Toronto, Ontario, Canada'}]}, { 'given': 'Christina T.', 'family': 'Saunders', 'sequence': 'additional', 'affiliation': [{'name': 'Berry Consultants, Austin, Texas'}]}, { 'given': 'Ary', 'family': 'Serpa-Neto', 'sequence': 'additional', 'affiliation': [ {'name': 'Monash University, Melbourne, Victoria, Australia'}, {'name': 'Hospital Israelita Albert Einstein, Sao Paulo, Brazil'}]}, { 'given': 'Christopher W.', 'family': 'Seymour', 'sequence': 'additional', 'affiliation': [{'name': 'University of Pittsburgh, Pittsburgh, Pennsylvania'}]}, { 'given': 'Manu', 'family': 'Shankar-Hari', 'sequence': 'additional', 'affiliation': [ {'name': 'King’s College London, London, England'}, {'name': 'Guy’s and St Thomas’ NHS Foundation Trust, London, England'}]}, { 'given': 'Vanessa', 'family': 'Singh', 'sequence': 'additional', 'affiliation': [{'name': 'Monash University, Melbourne, Victoria, Australia'}]}, { 'given': 'Timo', 'family': 'Tolppa', 'sequence': 'additional', 'affiliation': [ { 'name': 'National Intensive Care Surveillance (NICST), Colombo, Sri ' 'Lanka'}]}, { 'given': 'Alexis F.', 'family': 'Turgeon', 'sequence': 'additional', 'affiliation': [ {'name': 'Université Laval, Québec City, Québec, Canada'}, { 'name': 'CHU de Québec–Université Laval Research Center, Québec City, ' 'Québec, Canada'}]}, { 'given': 'Anne M.', 'family': 'Turner', 'sequence': 'additional', 'affiliation': [ { 'name': 'Medical Research Institute of New Zealand (MRINZ), Wellington, ' 'New Zealand'}]}, { 'given': 'Frank L.', 'family': 'van de Veerdonk', 'sequence': 'additional', 'affiliation': [{'name': 'Radboud University Medical Center, Nijmegen, the Netherlands'}]}, { 'given': 'Cameron', 'family': 'Green', 'sequence': 'additional', 'affiliation': [{'name': 'Monash University, Melbourne, Victoria, Australia'}]}, { 'given': 'Roger J.', 'family': 'Lewis', 'sequence': 'additional', 'affiliation': [ {'name': 'Berry Consultants, Austin, Texas'}, {'name': 'Harbor-UCLA Medical Center, Torrance, California'}]}, { 'given': 'Derek C.', 'family': 'Angus', 'sequence': 'additional', 'affiliation': [{'name': 'University of Pittsburgh, Pittsburgh, Pennsylvania'}]}, { 'given': 'Colin J.', 'family': 'McArthur', 'sequence': 'additional', 'affiliation': [{'name': 'Auckland City Hospital, Auckland, New Zealand'}]}, { 'given': 'Scott', 'family': 'Berry', 'sequence': 'additional', 'affiliation': [{'name': 'Berry Consultants, Austin, Texas'}]}, { 'given': 'Lennie P. G.', 'family': 'Derde', 'sequence': 'additional', 'affiliation': [{'name': 'University Medical Center Utrecht, Utrecht, the Netherlands'}]}, { 'given': 'Steve A.', 'family': 'Webb', 'sequence': 'additional', 'affiliation': [ {'name': 'Monash University, Melbourne, Victoria, Australia'}, {'name': 'St John of God Hospital, Subiaco, Western Australia, Australia'}]}, { 'given': 'Anthony C.', 'family': 'Gordon', 'sequence': 'additional', 'affiliation': [ {'name': 'Imperial College London, London, England'}, { 'name': 'Imperial College Healthcare NHS Trust, St Mary’s Hospital, ' 'London, England'}]}], 'member': '10', 'reference': [ { 'issue': '23', 'key': 'joi220025r1', 'doi-asserted-by': 'publisher', 'first-page': '2950', 'DOI': '10.1016/j.jacc.2020.04.031', 'article-title': 'COVID-19 and thrombotic or thromboembolic disease: implications for ' 'prevention, antithrombotic therapy, and follow-up: JACC ' 'state-of-the-art review.', 'volume': '75', 'author': 'Bikdeli', 'year': '2020', 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with novel coronavirus pneumonia.', 'volume': '18', 'author': 'Tang', 'year': '2020', 'journal-title': 'J Thromb Haemost'}, { 'key': 'joi220025r32', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.lfs.2020.118617', 'article-title': 'Preventing the development of severe COVID-19 by modifying ' 'immunothrombosis.', 'volume': '264', 'author': 'Morris', 'year': '2021', 'journal-title': 'Life Sci'}, { 'issue': '3', 'key': 'joi220025r33', 'doi-asserted-by': 'publisher', 'first-page': '212', 'DOI': '10.1159/000453002', 'article-title': 'Immunothrombosis in acute respiratory distress syndrome: cross talks ' 'between inflammation and coagulation.', 'volume': '93', 'author': 'Frantzeskaki', 'year': '2017', 'journal-title': 'Respiration'}, { 'issue': '3', 'key': 'joi220025r34', 'doi-asserted-by': 'publisher', 'first-page': '459', 'DOI': '10.1111/bjh.v192.3', 'article-title': 'Debate: should the dose or duration of anticoagulants for the ' 'prevention of venous thrombosis be increased in patients with COVID-19 ' 'while we are awaiting the results of clinical trials?', 'volume': '192', 'author': 'Gomez', 'year': '2021', 'journal-title': 'Br J Haematol'}, { 'issue': '2400', 'key': 'joi220025r35', 'doi-asserted-by': 'crossref', 'first-page': 'n2400', 'DOI': '10.1136/bmj.n2400', 'article-title': 'Effectiveness of therapeutic heparin vs prophylactic heparin on death, ' 'mechanical ventilation, or intensive care unit admission in moderately ' 'ill patients with COVID-19 admitted to hospital: RAPID randomised ' 'clinical trial.', 'volume': '375', 'author': 'Sholzberg', 'year': '2021', 'journal-title': 'BMJ'}, { 'issue': '12', 'key': 'joi220025r36', 'doi-asserted-by': 'publisher', 'first-page': '1612', 'DOI': '10.1001/jamainternmed.2021.6203', 'article-title': 'Efficacy and safety of therapeutic-dose heparin vs standard ' 'prophylactic or intermediate-dose heparins for thromboprophylaxis in ' 'high-risk hospitalized patients with COVID-19: the HEP-COVID randomized ' 'clinical trial.', 'volume': '181', 'author': 'Spyropoulos', 'year': '2021', 'journal-title': 'JAMA Intern Med'}, { 'issue': '16', 'key': 'joi220025r37', 'doi-asserted-by': 'crossref', 'first-page': '1620', 'DOI': '10.1001/jama.2021.4152', 'article-title': 'Effect of intermediate-dose vs standard-dose prophylactic ' 'anticoagulation on thrombotic events, extracorporeal membrane ' 'oxygenation treatment, or mortality among patients with COVID-19 ' 'admitted to the intensive care unit: the INSPIRATION randomized ' 'clinical trial.', 'volume': '325', 'author': 'Sadeghipour', 'year': '2021', 'journal-title': 'JAMA'}, { 'issue': '10291', 'key': 'joi220025r38', 'doi-asserted-by': 'publisher', 'first-page': '2253', 'DOI': '10.1016/S0140-6736(21)01203-4', 'article-title': 'Therapeutic versus prophylactic anticoagulation for patients admitted ' 'to hospital with COVID-19 and elevated D-dimer concentration (ACTION): ' 'an open-label, multicentre, randomised, controlled trial.', 'volume': '397', 'author': 'Lopes', 'year': '2021', 'journal-title': 'Lancet'}, { 'issue': '2', 'key': 'joi220025r39', 'doi-asserted-by': 'publisher', 'first-page': '131', 'DOI': '10.1016/j.thromres.2013.07.002', 'article-title': 'Use of antiplatelet agents in sepsis: a glimpse into the future.', 'volume': '133', 'author': 'Akinosoglou', 'year': '2014', 'journal-title': 'Thromb Res'}, { 'issue': '4', 'key': 'joi220025r40', 'doi-asserted-by': 'publisher', 'first-page': '930', 'DOI': '10.1213/ANE.0000000000005292', 'article-title': 'Aspirin use is associated with decreased mechanical ventilation, ' 'intensive care unit admission, and in-hospital mortality in ' 'hospitalized patients with coronavirus disease 2019.', 'volume': '132', 'author': 'Chow', 'year': '2021', 'journal-title': 'Anesth Analg'}, { 'issue': '2', 'key': 'joi220025r41', 'doi-asserted-by': 'publisher', 'first-page': '198', 'DOI': '10.1111/his.v77.2', 'article-title': 'Postmortem examination of COVID-19 patients reveals diffuse alveolar ' 'damage with severe capillary congestion and variegated findings in ' 'lungs and other organs suggesting vascular dysfunction.', 'volume': '77', 'author': 'Menter', 'year': '2020', 'journal-title': 'Histopathology'}, { 'issue': '3', 'key': 'joi220025r42', 'doi-asserted-by': 'publisher', 'first-page': '227', 'DOI': '10.1001/jama.2021.23605', 'article-title': 'Effect of P2Y12 inhibitors on survival free of organ support among ' 'non–critically ill hospitalized patients with COVID-19: a randomized ' 'clinical trial.', 'volume': '327', 'author': 'Berger', 'year': '2022', 'journal-title': 'JAMA'}, { 'issue': '3', 'key': 'joi220025r43', 'doi-asserted-by': 'publisher', 'first-page': '223', 'DOI': '10.1001/jama.2021.23866', 'article-title': 'Antiplatelet therapy in patients with COVID-19—more is less?', 'volume': '327', 'author': 'Spaetgens', 'year': '2022', 'journal-title': 'JAMA'}], 'container-title': 'JAMA', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://jamanetwork.com/journals/jama/articlepdf/2790488/jama_bradbury_2022_oi_220025_1648650455.00328.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 4, 5]], 'date-time': '2022-04-05T15:02:39Z', 'timestamp': 1649170959000}, 'score': 1, 'resource': {'primary': {'URL': 'https://jamanetwork.com/journals/jama/fullarticle/2790488'}}, 'subtitle': ['A Randomized Clinical Trial'], 'short-title': [], 'issued': {'date-parts': [[2022, 4, 5]]}, 'references-count': 43, 'journal-issue': {'issue': '13', 'published-print': {'date-parts': [[2022, 4, 5]]}}, 'URL': 'http://dx.doi.org/10.1001/jama.2022.2910', 'relation': {}, 'ISSN': ['0098-7484'], 'subject': ['General Medicine'], 'container-title-short': 'JAMA', 'published': {'date-parts': [[2022, 4, 5]]}}

Late treatment
is less effective

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

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