Heparin for Moderately Ill Patients with Covid-19
Michelle Sholzberg, Grace H Tang, Hassan Rahhal, Musaad AlHamzah, Lisa Baumann Kreuziger, Fionnuala Ní Áinle, Faris Alomran, Khalid Alayed, Mohammed Alsheef, Fahad AlSumait, Carlos Eduardo Pompilio, Catherine Sperlich, Sabrena Tangri, Terence Tang, Peter Jaksa, Deepa Suryanarayan, Mozah Almarshoodi, Lana Castellucci, Paula D James, David Lillicrap, Marc Carrier, Andrew Beckett, Christos Colovos, Jai Jayakar, Marie-Pier Arsenault, Cynthia Wu, Karine Doyon, E Roseann Andreou, Vera Dounaevskaia, Eric K Tseng, Gloria Lim, Michael Fralick, Saskia Middeldorp, Agnes Y Y Lee, Fei Zuo, Bruno R da Costa, Kevin E Thorpe, Elnara Márcia Negri, Mary Cushman, Peter Jüni, RAPID Trial investigators, Michelle Sholzberg, Grace H Tang, Hassan Rahhal, Musaad AlHamzah, Lisa Baumann Kreuziger, Fionnuala Ní Áinle, Faris Alomran, Khalid Alayed, Mohammed Alsheef, Fahad AlSumait, Carlos Eduardo Pompilio, Catherine Sperlich, Sabrena Tangri, Terence Tang, Peter Jaksa, Deepa Suryanarayan, Mozah Almarshoodi, Lana Castellucci, Paula D James, David Lillicrap, Marc Carrier, Andrew Beckett, Christos Colovos, Jai Jayakar, Marie-Pier Arsenault, Cynthia Wu, Karine Doyon, E Roseann Andreou, Vera Dounaevskaia, Eric K Tseng, Gloria Lim, Michael Fralick, Saskia Middeldorp, Agnes Y Y Lee, Fei Zuo, Bruno R da Costa, Kevin E Thorpe, Elnara Márcia Negri, Mary Cushman, Peter Jüni, RAPID Trial investigators
Abstract
Background: Heparin, in addition to its anticoagulant properties, has anti-inflammatory and potential anti-viral effects, and may improve endothelial function in patients with Covid-19. Early initiation of therapeutic heparin could decrease the thrombo-inflammatory process, and reduce the risk of critical illness or death.
Methods: We randomly assigned moderately ill hospitalized ward patients admitted for Covid-19 with elevated D-dimer level to therapeutic or prophylactic heparin. The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation or ICU admission. Safety outcomes included major bleeding. Analysis was by intention-to-treat.
Results: At 28 days, the primary composite outcome 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). Four patients (1.8%) assigned to therapeutic heparin died compared with 18 patients (7.6%) assigned to prophylactic heparin (odds ratio, 0.22; 95%-CI, 0.07 to 0.65). 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). Major bleeding occurred in 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).
Conclusions: 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. Trial registration numbers: NCT04362085 ; NCT04444700.
Source: PubMed