Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

Link to article at PubMed

N Engl J Med. 2021 Aug 4. doi: 10.1056/NEJMoa2105911. Online ahead of print.


BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.

METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.

RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.

CONCLUSIONS: In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP numbers, NCT04372589, NCT04505774, NCT02735707, and NCT04359277.).

PMID:34351721 | DOI:10.1056/NEJMoa2105911

One Comment

  1. I think patients with “real” covid that are NOT critically ill that will likely be inpatient for multiple days, aren’t on dual antiplatelets and do not have a “high-risk” of bleeding should receive therapeutic enoxaparin. If the patient ends up going to the ICU, the anticoagulant dose should be decreased to prophylactic dosing.

    (I define “real” covid as patients being admitted for symptomatic covid infection primarily affecting the respiratory system. That is, those that are asymptomatic, have very mild symptoms like mild diarrhea, or are being admitted for something else and are incidentally covid positive but either asymptomatic or mild should not get therapeutic enoxaparin.)

    (Also, the definition of “high-risk” of bleeding is very nebulous, and I suspect that led to many excluded patients.)

    Like the trials (as most screened patients were excluded for various reasons), I’d agree that most patients admitted with a covid+ test should not be on therapeutic enoxaparin. But, most patients admitted with “real” covid to a regular medical floor should be. Hope that makes sense.

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