Heparin for Moderately Ill Patients with Covid-19

Sholzberg, M.; Tang, G. H.; Rahhal, H.; AlHamzah, M.; Baumann Kreuziger, L.; Ni Ainle, F.; Alomran, F.; Alayed, K.; AlSheef, M.; AlSumait, F.; Pompilio, C. E.; Sperlich, C.; Tangri, S.; Tang, T.; Jaksa, P. J.; Suryanarayan, D.; Almarshoodi, M. O.; Castellucci, L. A.; James, P. D.; Lillicrap, D.; Carrier, M.; Beckett, A.; Colovos, C.; Jayakar, J.; Arsenault, M.-P.; Wu, C.; Doyon, K.; Andreou, E. R.; Dounaevskaia, V.; Tseng, E. K.; Lim, G.; Fralick, M.; Middeldorp, S.; Lee, A. Y. Y.; Zuo, F.; da Costa, B. R.; Thorpe, K. E.; Negri, E. M.; Cushman, M.; Jüni, P.; investigators, RAPID Trial

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.