Prophylactic Enoxaparin in Severe COVID-19: Standard vs Intermediate Dose

Two healthcare workers talking at the UCI
Researchers conducted a multi-center, open-label, randomized controlled trial to compare the effects of enoxaparin at the standard prophylactic dose with the intermediate dose for the treatment of adult patients with severe COVID-19.

In adult patients hospitalized with severe COVID-19, no differences were reported in 30-day mortality, thrombosis, or major bleeding outcomes following treatment with either the standard prophylactic dose or intermediate dose of enoxaparin, according to study results published in the Journal of Thrombosis and Haemostasis.

In this open-label, randomized controlled trial conducted at 3 centers in the United States, researchers compared treatment with enoxaparin at the standard prophylactic dose (40 mg/d) with the intermediate dose (1 mg/kg/d) in adult patients hospitalized with severe COVID-19. Patients were randomly assigned in a 1:1 fashion to receive either the standard or intermediate dose of enoxaparin; dose adjustments were made in both treatment groups according to weight. The primary outcome was all-cause mortality at 30 days; secondary outcomes were arterial or venous thromboembolism and major bleeding.

Of the 176 patients (median age, 64 years) enrolled in the study, 56% were men, 76% were White, 61% had a BMI greater than 30, 62% were admitted to an intensive care unit (ICU), and 23% underwent mechanical ventilation. Pre-existing conditions included hypertension (60%), current or former smoker (42%), diabetes (37%), heart disease (31%), and lung disease (23%).

The intention-to-treat population included 173 patients. Of those patients, 86 received the standard dose and 87 received the intermediate dose. All-cause 30-day mortality was 21% in the standard treatment group and 15% in the intermediate treatment group (odds ratio [OR], 0.66; 95% CI, 0.30-1.45; P =.31). The unadjusted model showed no significant difference in mortality between either treatment group, and no additional changes were noted after adjusting for age, sex, BMI, and ICU admission (hazard ratio, 0.57; 95% CI, 0.28-1.17; P =.123).

There were also no significant differences in secondary outcomes between patients in either treatment group:

  • Arterial thrombosis: 3% vs 6% (OR, 1.69; 95% CI, 0.39-7.29; P =.72).
  • Venous thrombosis: 7% vs 8% (OR, 1.79; 95% CI, 0.51-6.25; P >.99).
  • Major bleeding: 2% vs 2% (OR, 0.99; 95% CI, 0.14-7.14; P >.99).

The researchers noted that the results of this “study cannot be extrapolated to all patients hospitalized with COVID-19” because more than 85% of the screened patients did not meet the eligibility criteria.  Because outcomes beyond 30 days were not examined, the researchers concluded that “additional studies are needed to confirm our findings and assess the impact of anticoagulation therapy on the long-term effects of COVID-19.”

Disclosure: Some study author(s) declared affiliations with pharmaceutical, publishing, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Perepu US, Chambers I, Wahab A, et al. Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID-19: A multi-center, open-label, randomized controlled trial. J Thromb Haemost. Published online July 8, 2021. doi:10.1111/jth.15450

This article originally appeared on Infectious Disease Advisor