Antithrombotic Prophylaxis with Rivaroxaban in Patients with Prehospital COVID-19: A Meta-analysis of Two Placebo-Controlled Trials.

Autor:	Hsia J; Colorado Prevention Center and Department of Medicine, University of Colorado, Aurora, Colorado, United States., Spyropoulos AC; Feinstein Institutes for Medical Research and Department of Medicine, Northwell Health, New York, New York, United States., Piazza G; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States., Weng S; Janssen Research and Development, Statistical Decision Sciences, Cardiovascular and Metabolism, High Wycombe, United Kingdom., Dunne MW; Bill and Melinda Gates Medical Research Institute, Cambridge, Massachusetts, United States., Lipardi C; Janssen Research and Development, Clinical Development, Raritan, New Jersey, United States., Barnathan ES; Janssen Research and Development, Clinical Development, Raritan, New Jersey, United States., Bonaca MP; Colorado Prevention Center and Department of Medicine, University of Colorado, Aurora, Colorado, United States.
Jazyk:	angličtina
Zdroj:	Thrombosis and haemostasis [Thromb Haemost] 2024 Jul; Vol. 124 (7), pp. 649-655. Date of Electronic Publication: 2023 Nov 23.
DOI:	10.1055/a-2216-5848
Abstrakt:	Background:  We conducted a prespecified meta-analysis of two randomized, placebo-controlled trials of rivaroxaban 10 mg daily in prehospital patients with acute coronavirus disease 2019 (COVID-19). Individually, the trials had limited power to detect a treatment effect due to recruitment stopping ahead of plan. Material and Methods:  The statistical analysis plan for the meta-analysis was finalized before unblinding of PREVENT-HD, the larger of the two trials. Pooled risk ratios and pooled risk differences along with the two-sided 95% confidence intervals were calculated using random-effect models. Results:  Rivaroxaban did not reduce the occurrence of either the primary prespecified endpoint, a composite of symptomatic arterial and venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, all-cause hospitalization, and all-cause mortality (risk difference: 0.0044; 95% confidence interval: -0.0263, 0.0175; p  = 0.69 for pooled risk difference) or the secondary endpoint of all-cause hospitalization ( p  = 0.76). Although thrombotic events were infrequent, pooled analysis did reveal that rivaroxaban reduced arterial and venous thrombotic events (placebo 6 events, rivaroxaban 0 events; pooled risk difference: -0.0068; 95% confidence interval: -0.0132, -0.0006; p  = 0.03). In the pooled studies, only one major bleeding event was observed in a rivaroxaban-allocated patient with no critical site or fatal bleeding events. Conclusion:  Although this meta-analysis does not support antithrombotic prophylaxis with rivaroxaban in a broad prehospital population with acute COVID-19, the prevention of arterial and venous thrombotic events among rivaroxaban-allocated patients is consistent with the known thromboprophylactic effect of the drug in medically ill patients. Competing Interests: J.H. and M.P.B. receive salary support from CPC, a nonprofit academic research organization affiliated with the University of Colorado, that receives research grant/consulting funding from: Agios Pharmaceuticals, Inc., Alexion Pharma Godo Kaisha, Amgen Inc., Anthos Therapeutics, Inc., ARCA Biopharma, Inc., AstraZeneca Pharma India, AstraZeneca Pharmaceuticals LP, AstraZeneca UK Ltd, AstraZeneca, Produtos Farmaceuticos, Lda, Atentiv, LLC, Bayer, Bayer (Proprietary) Limited, Bayer Aktiengesellschaft, Bayer Pharma AG, Beth Israel Deaconess Medical Center, Better Therapeutics, Bionest Partners Inc., Boston Clinical Research Institute, LLC, Bristol-Myers Squibb, CellResearch Corporation Pte Ltd, Cleerly, Inc., Colorado Department of Public Health and Environment, Cook Regentec LLC, CSL Behring LLC, Eidos Therapeutics, Inc., EPG Communication Holdings Ltd, Esperion Therapeutics, Inc., Faraday Pharmaceuticals, Inc., HeartFlow Inc., Hummingbird Bioscience PTE. Ltd., Insmed, Ionis Pharmaceuticals, IQVIA Inc., Janssen Pharmaceuticals, Inc., Janssen Research & Development, LLC, Janssen Scientific Affairs LLC, Lexicon Pharmaceuticals, Inc., LSG Corporation, MedImmune Limited, Medpace, Inc., Medscape, Merck Sharp & Dohme Corp., Northwell Health, Novartis Pharmaceuticals Corporation, Novo Nordisk, Osiris Therapeutics, Inc., Pfizer, PPD Development, L.P., Prothena Biosciences Limited, Regeneron, Regents of the University of Colorado, Sanifit Therapeutics S.A., Sanofi, Silence Therapeutics PLC, Stanford University, Stealth BioTherapeutics Inc., The Brigham & Women's Hospital, Inc., Thrombosis Research Institute, UCD iC42 Laboratory, University of Colorado Denver, University of Pittsburgh, VarmX, WraSer, LLC. J.H. also reports owning AstraZeneca stock. A.C.S. has received research support from Boehringer Ingelheim, Janssen and AstraZeneca and consulting fees from Janssen, Bristol-Meyer Squibb/Pfizer Alliance, Sanofi, Alexion, Boehringer Ingelheim, Bayer, Roche Diagnostics, AstraZeneca. G.P. has received research support from Bristol-Myers Squibb/Pfizer Alliance, Bayer, Janssen, Alexion, Amgen and Boston Scientific Corporation, and consulting fees from Bristol-Myers Squibb/Pfizer Alliance, Boston Scientific Corporation, Janssen, NAMSA, Prairie Education and Research Cooperative, Boston Clinical Research Institute, and Amgen. M.W.D. reports no potential conflict of interest. S.W., C.L., and E.S.B. were employees of Janssen Research and Development during the conduct of PREVENT-HD. M.P.B. receives support from the AHA SFRN under award numbers 18SFRN3390085 (BWH-DH SFRN Center) and 18SFRN33960262 (BWH-DH Clinical Project) and also reports stock in Medtronic and Pfizer. (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu