Enoxaparin for symptomatic COVID-19 managed in the ambulatory setting: An individual patient level analysis of the OVID and ETHIC trials.

Anticoagulation COVID-19 Death Trial Venous thromboembolism

Journal

Thrombosis research
ISSN: 1879-2472
Titre abrégé: Thromb Res
Pays: United States
ID NLM: 0326377

Informations de publication

Date de publication:
Oct 2023
Historique:
received: 25 06 2023
revised: 09 08 2023
accepted: 14 08 2023
pubmed: 25 8 2023
medline: 25 8 2023
entrez: 25 8 2023
Statut: ppublish

Résumé

Antithrombotic treatment may improve the disease course in non-critically ill, symptomatic COVID-19 outpatients. We performed an individual patient-level analysis of the OVID and ETHIC randomized controlled trials, which compared enoxaparin thromboprophylaxis for either 14 (OVID) or 21 days (ETHIC) vs. no thromboprophylaxis for outpatients with symptomatic COVID-19 and at least one additional risk factor. The primary efficacy outcome included all-cause hospitalization and all-cause death within 30 days from randomization. Both studies were prematurely stopped for futility. Secondary efficacy outcomes were major symptomatic venous thromboembolic events, arterial cardiovascular events, or their composite occurring within 30 days from randomization. The same outcomes were assessed over a 90-day follow-up. The primary safety outcome was major bleeding (ISTH criteria). A total of 691 patients were randomized: 339 to receive enoxaparin and 352 to the control group. Over 30-day follow-up, the primary efficacy outcome occurred in 6.0 % of patients in the enoxaparin group vs. 5.8 % of controls for a risk ratio (RR) of 1.05 (95%CI 0.57-1.92). The incidence of major symptomatic venous thromboembolic events and arterial cardiovascular events was 0.9 % vs. 1.8 %, respectively (RR 0.52; 95%CI 0.13-2.06). Most cardiovascular thromboembolic events were represented by symptomatic venous thromboembolic events, occurring in 0.6 % vs. 1.5 % of patients, respectively. A similar distribution of outcomes between the treatment groups was observed over 90 days. No major bleeding occurred in the enoxaparin group vs. one (0.3 %) in the control group. We found no evidence for the clinical benefit of early administration of enoxaparin thromboprophylaxis in outpatients with symptomatic COVID-19. These results should be interpreted taking into consideration the relatively low occurrence of events.

Sections du résumé

BACKGROUND BACKGROUND
Antithrombotic treatment may improve the disease course in non-critically ill, symptomatic COVID-19 outpatients.
METHODS METHODS
We performed an individual patient-level analysis of the OVID and ETHIC randomized controlled trials, which compared enoxaparin thromboprophylaxis for either 14 (OVID) or 21 days (ETHIC) vs. no thromboprophylaxis for outpatients with symptomatic COVID-19 and at least one additional risk factor. The primary efficacy outcome included all-cause hospitalization and all-cause death within 30 days from randomization. Both studies were prematurely stopped for futility. Secondary efficacy outcomes were major symptomatic venous thromboembolic events, arterial cardiovascular events, or their composite occurring within 30 days from randomization. The same outcomes were assessed over a 90-day follow-up. The primary safety outcome was major bleeding (ISTH criteria).
RESULTS RESULTS
A total of 691 patients were randomized: 339 to receive enoxaparin and 352 to the control group. Over 30-day follow-up, the primary efficacy outcome occurred in 6.0 % of patients in the enoxaparin group vs. 5.8 % of controls for a risk ratio (RR) of 1.05 (95%CI 0.57-1.92). The incidence of major symptomatic venous thromboembolic events and arterial cardiovascular events was 0.9 % vs. 1.8 %, respectively (RR 0.52; 95%CI 0.13-2.06). Most cardiovascular thromboembolic events were represented by symptomatic venous thromboembolic events, occurring in 0.6 % vs. 1.5 % of patients, respectively. A similar distribution of outcomes between the treatment groups was observed over 90 days. No major bleeding occurred in the enoxaparin group vs. one (0.3 %) in the control group.
CONCLUSIONS CONCLUSIONS
We found no evidence for the clinical benefit of early administration of enoxaparin thromboprophylaxis in outpatients with symptomatic COVID-19. These results should be interpreted taking into consideration the relatively low occurrence of events.

Identifiants

DOI: 10.1016/j.thromres.2023.08.009 PMID: 37625200
pubmed: 37625200
pii: S0049-3848(23)00235-9
doi: 10.1016/j.thromres.2023.08.009
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

27-32

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Stefano Barco reports grants or contracts from Bayer, INARI, Boston Scientific, Medtronic, Bard, Sanofi, and Concept Medical; consulting fees from INARI; payment or honoraria from INARI, Boston Scientific, Penumbra and Concept Medical; and support for attending meetings and/or travel from Bayer and Sanofi. Roland Bingisser reports no conflicts of interest. Stefan Stortecky has received research grants to the institution from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific and Guerbet AG and speaker fees from Boston Scientific. Giuseppe Colucci reports no conflicts of interest. Bernhard Gerber reports non-financial support and funding for an accredited continuing medical education programme from Axonlab, and Thermo Fisher Scientific; personal fees and funding for an accredited continuing medical education programme from Alnylam, Pfizer, and Sanofi; funding for an accredited continuing medical education programme from Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Takeda, Octapharma, SOBI, Janssen, Novo Nordisk, Mitsubishi Pfizer, Tanabe Pharma, outside the submitted work. Jelle C L Himmelreich reports no conflicts of interest. DS reports employment by Sanofi-Aventis Switzerland. Thomas Rosemann reports no conflicts of interest. Walter Ageno reports research grants from Bayer; advisory boards for Bayer, Leo Pharma, Norgine, Sanofi, Techdow, Viatris. Juan Ignacio Arcelus declares speaker fees from Sanofi and Rovi. H.G reports personal fees from Pfizer, Bayer, Boehringer Ingelheim. Peter MacCallum reports no conflicts of interest. Daniel Duerschmied has received consulting fees from Boston Scientific and speakers' honoraria from Bayer, Daiichi Sankyo, Boston Scientific, Boehringer Ingelheim, and BMS/Pfizer. Tim Sebastian reports no conflicts of interest. Sylvia Haas reports honoraria from Bayer, BMS, Daiichi-Sankyo, Pfizer and Sanofi. Lukas Hobohm received lecture/consultant fees from Johnson&Johnson, INARI, MSD and Boston Scientific; outside the submitted work. The other authors report no conflicts of interest. Renato D Lopes reports research grants or contracts from Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, Sanofi-Aventis; funding for educational activities or lectures from Pfizer, Bristol-Myers Squibb, Novo Nordisk, AstraZeneca, and unding for consulting from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Novo Nordisk, AstraZeneca.

Auteurs

Stefano Barco (S)

Department of Angiology, University Hospital Zurich, Zurich, Switzerland; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University Mainz, Germany. Electronic address: stefano.barco@usz.ch.

Saverio Virdone (S)

Thrombosis Research Institute, London, UK.

Andrea Götschi (A)

Department of Biostatistics at Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Switzerland.

Walter Ageno (W)

Department of Medicine and Surgery, University of Insubria, Varese, Italy.

Juan I Arcelus (JI)

Department of Surgery, University of Granada, Granada, Spain.

Roland Bingisser (R)

Emergency Department, University Hospital Basel, Basel, Switzerland.

Giuseppe Colucci (G)

Service of Hematology, Clinica Luganese Moncucco, Lugano, Switzerland; Department of Hematology, University of Basel, Basel, Switzerland; Clinica Sant'Anna, Sorengo, Switzerland.

Frank Cools (F)

Department of Cardiology, General Hospital Klina, Brasschaat, Belgium.

Daniel Duerschmied (D)

Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Germany; European Center for AngioScience (ECAS) and German Center for Cardiovascular Research (DZHK) partner site Heidelberg/Mannheim, Mannheim, Germany; Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Harry Gibbs (H)

Department of General Medicine, The Alfred Hospital, Melbourne, VIC, Australia.

Riccardo M Fumagalli (RM)

Department of Angiology, University Hospital Zurich, Zurich, Switzerland.

Bernhard Gerber (B)

Clinic of Hematology, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland; University of Zurich, Zurich, Switzerland.

Sylvia Haas (S)

Formerly Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Jelle C L Himmelreich (JCL)

Department of General Practice, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.

Richard Hobbs (R)

Oxford Primary Care, Radcliffe Observatory Quarter, University of Oxford, Oxford, UK; Cardiology Division, Geneva University Hospitals, Geneva, Switzerland.

Lukas Hobohm (L)

Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University Mainz, Germany.

Barry Jacobson (B)

Department of Haematology and Molecular Medicine, University of the Witwatersrand, Johannesburg, South Africa.

Gloria Kayani (G)

Thrombosis Research Institute, London, UK.

Renato D Lopes (RD)

Duke University Medical Center, Durham, USA; Brazilian Clinical Research Institute (BCRI), Sao Paulo, Brazil.

Peter MacCallum (P)

Wolfson Institute of Population Health, Queen Mary University of London, London, UK.

Evy Micieli (E)

Department of Angiology, University Hospital Zurich, Zurich, Switzerland.

Marc Righini (M)

Division of Angiology and Hemostasis, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Switzerland.

Helia Robert-Ebadi (H)

Division of Angiology and Hemostasis, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Switzerland.

Ana Thereza Rocha (AT)

Department of Family Health, Federal University of Bahia, Salvador, Brazil; D'Or Institute for Research and Education, Rio de Janeiro, Brazil.

Thomas Rosemann (T)

Institute of Primary Care, University Hospital Zurich, Zurich, Switzerland.

Jitendra Sawhney (J)

Department of Cardiology, Sir Ganga Ram Hospital, New Delhi, India.

Sebastian Schellong (S)

Department of Internal Medicine, Municipal Hospital Dresden, Dresden, Germany.

Tim Sebastian (T)

Department of Angiology, University Hospital Zurich, Zurich, Switzerland.

David Spirk (D)

Institute of Pharmacology, University of Bern, Bern, Switzerland.

Stefan Stortecky (S)

Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Switzerland.

Alexander G G Turpie (AGG)

Department of Medicine, McMaster University, Hamilton, ON, Canada.

Davide Voci (D)

Department of Angiology, University Hospital Zurich, Zurich, Switzerland.

Nils Kucher (N)

Department of Angiology, University Hospital Zurich, Zurich, Switzerland.

Karen Pieper (K)

Thrombosis Research Institute, London, UK.

Ulrike Held (U)

Department of Biostatistics at Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Switzerland.

Ajay K Kakkar (AK)

Thrombosis Research Institute, London, UK.

Classifications MeSH