Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial.

Autor:	Bikdeli B; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.; Yale/YNHH Center for Outcomes Research and Evaluation, New Haven, Connecticut, United States.; Cardiovascular Research Foundation, New York, New York, United States., Talasaz AH; Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran., Rashidi F; Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Bakhshandeh H; Clinical Trial Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran.; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical Sciences, Tehran, Iran., Rafiee F; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical Sciences, Tehran, Iran., Rezaeifar P; Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Baghizadeh E; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical Sciences, Tehran, Iran., Matin S; Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Jamalkhani S; Student Research Committee, Iran University of Medical Sciences, Tehran, Iran., Tahamtan O; Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Sharif-Kashani B; Tobacoo Prevention and Control Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Department of Cardiology, Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Beigmohammadi MT; Anesthesiology and Intensive Care, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran., Farrokhpour M; Department of Internal Medicine, Firouzgar Hospital, Iran University of Medical Sciences, Tehran, Iran., Sezavar SH; Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran., Payandemehr P; Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran., Dabbagh A; Department of Anesthesiology, School of Medicine Anesthesiology Research Center, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Moghadam KG; Department of Internal Medicine, School of Medicine, Shariati Hospital, Tehran, Iran., Khalili H; Department of Pharmacotherapy, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran., Yadollahzadeh M; Department of Internal Medicine, Firouzgar Hospital, Iran University of Medical Sciences, Tehran, Iran., Riahi T; Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran., Abedini A; Chronic Respiratory Disease Research Center, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Lookzadeh S; Chronic Respiratory Disease Research Center, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Rahmani H; Department of Pharmacotherapy, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran., Zoghi E; School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran., Mohammadi K; School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran., Sadeghipour P; Department of Internal Medicine, Firouzgar Hospital, Iran University of Medical Sciences, Tehran, Iran., Abri H; Department of Internal Medicine, Firouzgar Hospital, Iran University of Medical Sciences, Tehran, Iran., Tabrizi S; Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran., Mousavian SM; Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran., Shahmirzaei S; Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran., Amin A; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical Sciences, Tehran, Iran., Mohebbi B; Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran., Parhizgar SE; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical Sciences, Tehran, Iran., Aliannejad R; Department of Pulmonary and Critical Care, School of Medicine, Shariati Hospital, Tehran, Iran.; Advanced Thoracic Research Center, Tehran University of Medical Sciences, Tehran, Iran., Eslami V; Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Kashefizadeh A; Shahid Dr. Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Dobesh PP; College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, United States., Kakavand H; School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran., Hosseini SH; School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran., Shafaghi S; Department of Cardiology, Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Ghazi SF; Anesthesiology and Intensive Care, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran., Najafi A; Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran., Jimenez D; Respiratory Department, Hospital Ramón y Cajal, Madrid, Spain.; Medicine Department, Universidad de Alcalá, Madrid, Spain.; CIBER Enfermedades Respiratorias, Madrid, Spain., Gupta A; Yale/YNHH Center for Outcomes Research and Evaluation, New Haven, Connecticut, United States.; Cardiovascular Research Foundation, New York, New York, United States.; Division of Cardiology, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, New York, United States., Madhavan MV; Cardiovascular Research Foundation, New York, New York, United States.; Division of Cardiology, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, New York, United States., Sethi SS; Cardiovascular Research Foundation, New York, New York, United States.; Division of Cardiology, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, New York, United States., Parikh SA; Cardiovascular Research Foundation, New York, New York, United States.; Division of Cardiology, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, New York, United States., Monreal M; Department of Internal Medicine, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.; Universidad Católica de Murcia, Murcia, Spain., Hadavand N; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical Sciences, Tehran, Iran., Hajighasemi A; Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran., Maleki M; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical Sciences, Tehran, Iran., Sadeghian S; Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran., Piazza G; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States., Kirtane AJ; Cardiovascular Research Foundation, New York, New York, United States.; Division of Cardiology, Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, New York, New York, United States., Van Tassell BW; Department of Pharmacotherapy and Outcome Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, United States.; Division of Cardiology, Department of Internal Medicine, Pauley Heart Center, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, United States., Stone GW; Cardiovascular Research Foundation, New York, New York, United States.; The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States., Lip GYH; Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom.; Aalborg University, Aalborg, Denmark., Krumholz HM; Yale/YNHH Center for Outcomes Research and Evaluation, New Haven, Connecticut, United States.; Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, United States.; Department of Health Policy and Administration, Yale School of Public Health, New Haven, Connecticut, United States., Goldhaber SZ; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States., Sadeghipour P; Clinical Trial Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, Iran.; Rajaie Cardiovascular Medical and Research Center, Iran university of Medical Sciences, Tehran, Iran.; School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Jazyk:	angličtina
Zdroj:	Thrombosis and haemostasis [Thromb Haemost] 2022 Jan; Vol. 122 (1), pp. 131-141. Date of Electronic Publication: 2021 Jun 06.
DOI:	10.1055/a-1485-2372
Abstrakt:	Background: Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. Methods: This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. Results: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p  = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). Conclusion: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up. Competing Interests: Dr. Parikh reports being on the Advisory Board for Abbott, Boston Scientific, Medtronic, CSI, Philips, Janssen; research grants: Abbott, Boston Scientific, Surmodics, TriReme Medical, Shockwave Medical; and receiving consulting fees from Terumo and Abiomed. Dr. Gupta received payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation and from the Ben C. Martin Law Firm for work related to the Cook inferior vena cava filter litigation. Dr. Gupta holds equity in a health care telecardiology startup, Heartbeat Health, Inc. and received consulting fees from Edwards LifeSciences. Dr. Madhavan has received support from an institutional grant by the National Institutes of Health/National Heart, Lung, and Blood Institute to Columbia University Irving Medical Center (T32 HL007854). Dr. Sethi reports honoraria from Janssen and Chiesi and research grant support from the American Heart Association. Dr. Piazza has received research grant support to Brigham and Women's Hospital from EKOS, a BTG International Group company, Bayer, the Bristol Myers Squibb/Pfizer Alliance, Portola, and Janssen. He has received consulting fees from Amgen, Pfizer, Boston Scientific Corporation, and Thrombolex. Dr. Kirtane reports institutional funding to Columbia University and/or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, and ReCor Medical. In addition to research grants, institutional funding includes fees paid to Columbia University and/or Cardiovascular Research Foundation for speaking engagements and/or consulting. Personal: travel expenses/meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. Dr. Van Tassell received research support from Novartis, Swedish Orphan Biovitrum, Olatec Therapeutics, and Serpin Pharma. He is a consultant of R-Pharm, Serpin Pharma. Dr. Stone has received speaker or other honoraria from Cook, Terumo, and Orchestra Biomed; served as a consultant to Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, Matrizyme, Cardiomech; and has received equity or options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, MedFocus family of funds, and Valfix. Dr. Lip reports consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are received personally. Dr. Krumholz reports personal fees from UnitedHealth, personal fees from IBM Watson Health, personal fees from Element Science, personal fees from Aetna, personal fees from Facebook, personal fees from Siegfried & Jensen Law Firm, personal fees from Arnold & Porter Law Firm, personal fees from Ben C. Martin Law Firm, personal fees from National Center for Cardiovascular Diseases, Beijing, ownership of HugoHealth, ownership of Refactor Health, contracts from the Centers for Medicare & Medicaid Services, grants from Medtronic and the Food and Drug Administration, grants from Medtronic and Johnson and Johnson, grants from Shenzhen Center for Health Information, and is a Venture Partner at FPrime, outside the submitted work. Dr. Bikdeli reports that he is a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of IVC filters. All other authors report no relevant Enoxaparin was provided through Alborz Darou, Pooyesh Darou, and Caspian Pharmaceuticals companies, and atorvastatin and matching placebo were provided by Sobhan Darou. None of these companies were study sponsors and they had no other role and will not have a role in the design, conduct, analysis, or interpretation of the ongoing results or the decision to submit the resultant manuscript(s). (Thieme. All rights reserved.)
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