Enoxaparin for symptomatic COVID-19 managed in the ambulatory setting: An individual patient level analysis of the OVID and ETHIC trials
type: Article
item type: journalArticle
is part of: Thromb Res
authors: Person
  surname: Barco
  given name: S.
authors: Person
  surname: Virdone
  given name: S.
authors: Person
  surname: Gotschi
  given name: A.
authors: Person
  surname: Ageno
  given name: W.
authors: Person
  surname: Arcelus
  given name: J. I.
authors: Person
  surname: Bingisser
  given name: R.
authors: Person
  surname: Colucci
  given name: G.
authors: Person
  surname: Cools
  given name: F.
authors: Person
  surname: Duerschmied
  given name: D.
authors: Person
  surname: Gibbs
  given name: H.
authors: Person
  surname: Fumagalli
  given name: R. M.
authors: Person
  surname: Gerber
  given name: B.
authors: Person
  surname: Haas
  given name: S.
authors: Person
  surname: Himmelreich
  given name: J. C. L.
authors: Person
  surname: Hobbs
  given name: R.
authors: Person
  surname: Hobohm
  given name: L.
authors: Person
  surname: Jacobson
  given name: B.
authors: Person
  surname: Kayani
  given name: G.
authors: Person
  surname: Lopes
  given name: R. D.
authors: Person
  surname: MacCallum
  given name: P.
authors: Person
  surname: Micieli
  given name: E.
authors: Person
  surname: Righini
  given name: M.
authors: Person
  surname: Robert-Ebadi
  given name: H.
authors: Person
  surname: Rocha
  given name: A. T.
authors: Person
  surname: Rosemann
  given name: T.
authors: Person
  surname: Sawhney
  given name: J.
authors: Person
  surname: Schellong
  given name: S.
authors: Person
  surname: Sebastian
  given name: T.
authors: Person
  surname: Spirk
  given name: D.
subject: Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, Sanofi-Aventis
subject: Anticoagulation
subject: Arcelus declares speaker fees from Sanofi and Rovi. H.G reports personal fees
subject: Boston Scientific
subject: Covid-19
subject: Death
subject: Haas reports honoraria from Bayer, BMS, Daiichi-Sankyo, Pfizer and Sanofi. Lukas
subject: Hobohm received lecture/consultant fees from Johnson&Johnson, INARI, MSD and
subject: INARI
subject: Ingelheim, Bristol-Myers Squibb, Novo Nordisk, AstraZeneca.
subject: Ingelheim, and BMS/Pfizer. Tim Sebastian reports no conflicts of interest. Sylvia
subject: Medical
subject: Novo Nordisk, AstraZeneca, and unding for consulting from Bayer, Boehringer
subject: Pfizer, and Sanofi
subject: Roland Bingisser reports no conflicts of interest. Stefan Stortecky has received
subject: SOBI, Janssen, Novo Nordisk, Mitsubishi Pfizer, Tanabe Pharma, outside the
subject: Scientific, Medtronic, Bard, Sanofi, and Concept Medical
subject: Scientific. Giuseppe Colucci reports no conflicts of interest. Bernhard Gerber
subject: Trial
subject: Vascular, Boston Scientific and Guerbet AG and speaker fees from Boston
subject: Venous thromboembolism
subject: advisory
subject: and speakers' honoraria from Bayer, Daiichi Sankyo, Boston Scientific, Boehringer
subject: and support for attending meetings and/or travel from Bayer and Sanofi.
subject: boards for Bayer, Leo Pharma, Norgine, Sanofi, Techdow, Viatris. Juan Ignacio
subject: conflicts of interest. Renato D Lopes reports research grants or contracts from
subject: conflicts of interest. Walter Ageno reports research grants from Bayer
subject: consulting fees from
subject: education programme from Axonlab, and Thermo Fisher Scientific
subject: from Pfizer, Bayer, Boehringer Ingelheim. Peter MacCallum reports no conflicts of
subject: funding for an accredited continuing medical education
subject: funding for an accredited continuing medical education programme from Alnylam,
subject: funding for educational activities or lectures from Pfizer, Bristol-Myers Squibb,
subject: interest. Daniel Duerschmied has received consulting fees from Boston Scientific
subject: interests/personal relationships which may be considered as potential competing
subject: interests: Stefano Barco reports grants or contracts from Bayer, INARI, Boston
subject: outside the submitted work. The other authors report no
subject: payment or honoraria from INARI, Boston Scientific, Penumbra and Concept
subject: personal fees and
subject: programme from Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Takeda, Octapharma,
subject: reports employment by Sanofi-Aventis Switzerland. Thomas Rosemann reports no
subject: reports non-financial support and funding for an accredited continuing medical
subject: research grants to the institution from Edwards Lifesciences, Medtronic, Abbott
subject: submitted work. Jelle C L Himmelreich reports no conflicts of interest. DS
abstract: BACKGROUND: Antithrombotic treatment may improve the disease course in non-critically ill, symptomatic COVID-19 outpatients. 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: 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: 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.
date: 2023-08-25
pages: 27-32
coverage: 37625200

Thromb Res
type: Journal
volume: 230
identifier: DOI 10.1016/j.thromres.2023.08.009
identifier: ISSN 1879-2472 (Electronic) 0049-3848 (Linking)

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surname: Stortecky
given name: S.

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surname: Turpie
given name: A. G. G.

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given name: K.

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surname: Held
given name: U.

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surname: Kakkar
given name: A. K.

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surname: Ovid

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