Heparin in noncritically ill COVID-19 patients [Classics Series]

This study summary is an excerpt from the book 2 Minute Medicine’s The Classics in Medicine: Summaries of the Landmark Trials

1. This study found that in patients hospitalized, but not critically ill, with coronavirus disease 2019 (COVID-19), heparin treatment was associated with significantly more organ support–free days as compared to normal thromboprophylaxis (98.6% posterior probability).

2. Probability of survival until hospital discharge was also increased in group receiving heparin (87.1% posterior probability).

Original Date of Publication: August 2021

Study Rundown: In this clinical trial, therapeutic use of heparin was compared to standard thromboprophylaxis in hospitalized but noncritically ill COVID-19 patients. The heparin group had a significant increase in organ support-free days as well as increased survival to hospital discharge. The benefit of heparin was greater in patients with an elevated D-dimer level. The main limitation of this study was that it was open-label. In summary, the present clinical trial demonstrated that in noncritically ill patients with COVID-19, heparin was superior to standard thromboprophylaxis in reducing in-hospital mortality and requirement for end-stage organ support.

Click to read the study in NEJM

In-Depth [randomized control trial]: The present study randomized hospitalized COVID-19 patients with moderate disease to receive either anticoagulation with heparin (n = 1190) or pharmacologic thromboprophylaxis as usual (n = 1054). The primary endpoint of organ support-free days was measured as a combination of in-hospital mortality and time without cardiovascular or respiratory organ support.

Treatment with therapeutic doses of heparin significantly increased the number of organ support-free days was when compared to controls receiving thromboprophylaxis (OR 1.27; 95%CI 1.03-1.58). Patients treated with therapeutic heparin also experienced significantly higher survival until hospital discharge when compared to thromboprophylaxis (95%CI 0.5-7.2). Notably, the benefits of the therapeutic heparin was higher in patients with elevated D-dimer levels (97.3%) compared to those with a low D-dimer (92.9%). Rates of thrombotic events or in-hospital mortality were also lower in the heparin group (8.0%) than the control group (9.9%). Unsurprisingly, major bleeding was more common in the heparin group (1.9%) as compared to usual thromboprophylaxis (0.9%).

The ATTACC, ACTIV-4a, and REMAP-CAP Investigators. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with COVID-19. N Engl J Med. 2021 Aug 26;385(9):790–802.

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