Predictors of bleeding and thrombotic events among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomized clinical trial.
Anticoagulant
COVID-19
Haemorrhage
Thromboembolism
Journal
Journal of thrombosis and thrombolysis
ISSN: 1573-742X
Titre abrégé: J Thromb Thrombolysis
Pays: Netherlands
ID NLM: 9502018
Informations de publication
Date de publication:
18 May 2024
18 May 2024
Historique:
accepted:
26
04
2024
medline:
19
5
2024
pubmed:
19
5
2024
entrez:
18
5
2024
Statut:
aheadofprint
Résumé
Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.
Identifiants
pubmed: 38762708
doi: 10.1007/s11239-024-02995-y
pii: 10.1007/s11239-024-02995-y
doi:
Banques de données
ClinicalTrials.gov
['NCT04394377']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Ackermann M, Verleden SE, Kuehnel M et al (2020) Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Engl J Med 383:120–128
doi: 10.1056/NEJMoa2015432
pubmed: 32437596
pmcid: 7412750
Zhou F, Yu T, Du R et al (2020) Clinical course and risk factors for mortality of adult in patients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395:1054–1062
doi: 10.1016/S0140-6736(20)30566-3
pubmed: 32171076
pmcid: 7270627
Gungor B, Atici A, Baycan OF et al (2021) Elevated D-dimer levels on admission are associated with severity and increased risk of mortality in COVID-19: a systematic review and meta-analysis. Am J Emerg Med 39:173–179
doi: 10.1016/j.ajem.2020.09.018
pubmed: 33069541
Jiménez D, García-Sanchez A, Rali P et al (2021) Incidence of VTE and bleeding among hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis. Chest 159:1182–1196
doi: 10.1016/j.chest.2020.11.005
pubmed: 33217420
Shi S, Qin M, Shen B et al (2020) Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol 5:802–810
doi: 10.1001/jamacardio.2020.0950
pubmed: 32211816
pmcid: 7097841
Lopes RD, de Barros E, Silva PGM, Furtado RHM et al (2021) Randomized clinical trial to evaluate a routine full anticoagulation Strategy in Patients with Coronavirus Infection (SARS-CoV2) admitted to hospital: Rationale and design of the ACTION (AntiCoagulaTlon cOroNavirus)-Coalition IV trial. Am Heart J 238:1–11
doi: 10.1016/j.ahj.2021.04.005
pubmed: 33891907
pmcid: 8057688
Lopes RD, de Barros e Silva PGM, Furtado RHM et al (2021) Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet 397:2253–2263
doi: 10.1016/S0140-6736(21)01203-4
pubmed: 34097856
pmcid: 8177770
The REMAP-CAP, ACTIV-4a, and ATTACC Investigators (2021) Therapeutic anticoagulation with heparin in critically ill patients with COVID-19. N Engl J Med published online Aug 4. https://doi.org/10.1056/NEJMoa2103417
The ATTACC, ACTIV-4a, and REMAP-CAP Investigators (2021) Therapeutic anticoagulation with heparin in noncritically ill patients with COVID-19. N Engl J Med published online Aug 4. https://doi.org/10.1056/NEJMoa2105911
Bikdeli B, Talasaz AH, Rashidi F et al (2022) 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. Thromb Haemost 122(1):131–141
doi: 10.1055/a-1485-2372
pubmed: 33865239
Spyropoulos AC, Goldin M, Giannis D et al (2021) Efficacy and safety of therapeutic-dose heparin vs standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients With COVID-19: the HEP-COVID randomized clinical trial. JAMA Intern Med 181(12):1612–1620
doi: 10.1001/jamainternmed.2021.6203
pubmed: 34617959
pmcid: 8498934
Sholzberg M, Tang GH, Rahhal H et al (2021) Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial. BMJ 375:n2400
doi: 10.1136/bmj.n2400
pubmed: 34649864
Bohula EA, Berg DD, Lopes MS et al (2022) Anticoagulation and antiplatelet therapy for prevention of venous and arterial thrombotic events in critically Ill patients with COVID-19: COVID-PACT. Circulation 146(18):1344–1356
doi: 10.1161/CIRCULATIONAHA.122.061533
pubmed: 36036760
pmcid: 9624238
Stone GW, Farkouh ME, Lala A et al (2023) Randomized trial of anticoagulation strategies for noncritically ill patients hospitalized with COVID-19. J Am Coll Cardiol 81(18):1747–1762. https://doi.org/10.1016/j.jacc.2023.02.041
Kaatz S, Ahmad D, Spyropoulos AC et al (2015) Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 13:2119–2126
doi: 10.1111/jth.13140
pubmed: 26764429
Wattanakit K, Cushman M, Stehman-Breen C et al (2008) Chronic kidney disease increases risk for venous thromboembolism. J Am Soc Nephrol 19(1):135–140
doi: 10.1681/ASN.2007030308
pubmed: 18032796
pmcid: 2391038
Helms J, Tacquard C, Severac F et al (2020) High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 46(6):1089–1098
doi: 10.1007/s00134-020-06062-x
pubmed: 32367170
pmcid: 7197634