Enoxaparin for symptomatic COVID-19 managed in the ambulatory setting: An individual patient level analysis of the OVID and ETHIC trials - Barco, S.; Virdone, S.; Gotschi, A.; Ageno, W.; Arcelus, J. I.; Bingisser, R.; Colucci, G.; Cools, F.; Duerschmied, D.; Gibbs, H.; Fumagalli, R. M.; Gerber, B.; et al. (Thromb Res, 2023)
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.
Keywords: journalArticle; Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, Sanofi-Aventis; Anticoagulation; Arcelus declares speaker fees from Sanofi and Rovi. H.G reports personal fees; Boston Scientific; Covid-19; Death; Haas reports honoraria from Bayer, BMS, Daiichi-Sankyo, Pfizer and Sanofi. Lukas; Hobohm received lecture/consultant fees from Johnson&Johnson, INARI, MSD and; INARI; Ingelheim, Bristol-Myers Squibb, Novo Nordisk, AstraZeneca; Ingelheim, and BMS/Pfizer. Tim Sebastian reports no conflicts of interest. Sylvia; Medical; Novo Nordisk, AstraZeneca, and unding for consulting from Bayer, Boehringer; Pfizer, and Sanofi; Roland Bingisser reports no conflicts of interest. Stefan Stortecky has received; SOBI, Janssen, Novo Nordisk, Mitsubishi Pfizer, Tanabe Pharma, outside the; Scientific, Medtronic, Bard, Sanofi, and Concept Medical; Scientific. Giuseppe Colucci reports no conflicts of interest. Bernhard Gerber; Trial; Vascular, Boston Scientific and Guerbet AG and speaker fees from Boston; Venous thromboembolism; advisory; and speakers' honoraria from Bayer, Daiichi Sankyo, Boston Scientific, Boehringer; and support for attending meetings and/or travel from Bayer and Sanofi; boards for Bayer, Leo Pharma, Norgine, Sanofi, Techdow, Viatris. Juan Ignacio; conflicts of interest. Renato D Lopes reports research grants or contracts from; conflicts of interest. Walter Ageno reports research grants from Bayer; consulting fees from; education programme from Axonlab, and Thermo Fisher Scientific; from Pfizer, Bayer, Boehringer Ingelheim. Peter MacCallum reports no conflicts of; funding for an accredited continuing medical education; funding for an accredited continuing medical education programme from Alnylam,; funding for educational activities or lectures from Pfizer, Bristol-Myers Squibb,; interest. Daniel Duerschmied has received consulting fees from Boston Scientific; interests/personal relationships which may be considered as potential competing; interests: Stefano Barco reports grants or contracts from Bayer, INARI, Boston; outside the submitted work. The other authors report no; payment or honoraria from INARI, Boston Scientific, Penumbra and Concept; personal fees and; programme from Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Takeda, Octapharma,; reports employment by Sanofi-Aventis Switzerland. Thomas Rosemann reports no; reports non-financial support and funding for an accredited continuing medical; research grants to the institution from Edwards Lifesciences, Medtronic, Abbott; submitted work. Jelle C L Himmelreich reports no conflicts of interest. DS