Full Heparin Dose Improves Outcomes for Moderately Ill COVID-19 Patients

Use of a common blood thinner in hospitalized patients moderately ill with COVID-19 made a big difference in their risk of dying, according to a new study. Find out researchers came to that conclusion and their recommendations for future treatment.

TORONTO – Moderately ill patients hospitalized with COVID-19 fared better with a full dose of a standard blood thinner early in their disease progression, a new study points out.

Infection with novel coronavirus increases inflammation and causes abnormal clotting in the blood vessels, especially in the lungs – processes suspected of contributing to severe disease and death.

Canadian researchers from St. Michaels Hospital in Toronto worked with investigators from the University of Vermont Larner College of Medicine in the United States to conduct the trial. It found that administering a full dose of heparin early to moderately ill hospitalized patients with COVID-19 helps stem the thrombo-inflammation process and appears to lower the risk of severe disease and death.

"This study was designed to detect a difference in the primary outcome that included ICU transfer, mechanical ventilation or death," explained co-principal investigator Mary Cushman, MD, MSC, of the University of Vermont.

Study authors note that the anticoagulant heparin also has strong has potential anti-inflammatory and anti-viral effects. The hope was the commonly used agent might improve endothelial function in patients with COVID-19.

To find out, the study team randomly assigned moderately ill hospitalized ward patients admitted for COVID-19 with elevated D-dimer levels to therapeutic or prophylactic heparin. Defined as the primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation or intensive care admission. Researchers also looked at safety outcomes, including major bleeding.

Results of the open-label randomized international multi-center RAPID Trial (also known as the RAPID COVID COAG - RAPID Trial) indicate that, at 28 days, the primary composite outcome had occurred in 37 of 228 patients (16.2%) assigned to therapeutic heparin, and 52 of 237 patients (21.9%) assigned to prophylactic heparin (odds ratio, 0.69; 95% confidence interval [CI], 0.43 to 1.10; p=0.12).

The authors point out that four patients (1.8%) assigned to therapeutic heparin died vs. 18 patients (7.6%) assigned to prophylactic heparin (odds ratio, 0.22; 95%-CI, 0.07 to 0.65). In addition, the composite of all-cause mortality or any mechanical ventilation occurred in 23 (10.1%) in the therapeutic heparin group and 38 (16.0%) in the prophylactic heparin group (odds ratio, 0.59; 95%-CI, 0.34 to 1.02), they report.

In terms of safety, major bleeding occurred in only 2 patients (0.9%) with therapeutic heparin and 4 patients (1.7%) with prophylactic heparin (odds ratio, 0.52; 95%-CI, 0.09 to 2.85).

“In moderately ill ward patients with Covid-19 and elevated D-dimer level, therapeutic heparin did not significantly reduce the primary outcome but decreased the odds of death at 28 days,” the authors write.

"While we found that therapeutic heparin didn't statistically significantly lower incidence of the primary composite of death, mechanical ventilation or ICU admission compared with low dose heparin, the odds of all-cause death were significantly reduced by 78 percent with therapeutic heparin," explained first author and co-principal investigator Michelle Sholzberg, MDCM, MSC, of St. Michael's Hospital of Unity Health Toronto and the University of Toronto.

Sholzberg added, "We believe that the findings of our trial and the multiplatform trial taken together should result in a change in clinical practice for moderately ill ward patients with COVID-19."

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