Background: This study was conducted to evaluate the impact of low-molecular-weight heparin (LMWH) on the outcome of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Methods: This is a prospective observational study including consecutive patients with laboratory-confirmed SARS-CoV-2 pneumonia admitted to the University Hospital of Pisa (March 4-April 30, 2020). Demographic, clinical, and outcome data were collected. The primary endpoint was 30-day mortality. The secondary endpoint was a composite of death or severe acute respiratory distress syndrome (ARDS). Low-molecular-weight heparin, hydroxychloroquine, doxycycline, macrolides, antiretrovirals, remdesivir, baricitinib, tocilizumab, and steroids were evaluated as treatment exposures of interest. First, a Cox regression analysis, in which treatments were introduced as time-dependent variables, was performed to evaluate the association of exposures and outcomes. Then, a time-dependent propensity score (PS) was calculated and a PS matching was performed for each treatment variable. Results: Among 315 patients with SARS-CoV-2 pneumonia, 70 (22.2%) died during hospital stay. The composite endpoint was achieved by 114 (36.2%) patients. Overall, 244 (77.5%) patients received LMWH, 238 (75.5%) received hydroxychloroquine, 201 (63.8%) received proteases inhibitors, 150 (47.6%) received doxycycline, 141 (44.8%) received steroids, 42 (13.3%) received macrolides, 40 (12.7%) received baricitinib, 13 (4.1%) received tocilizumab, and 13 (4.1%) received remdesivir. At multivariate analysis, LMWH was associated with a reduced risk of 30-day mortality (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.21-0.6; P <.001) and composite endpoint (HR, 0.61; 95% CI, 0.39-0.95; P =.029). The PS-matched cohort of 55 couples confirmed the same results for both primary and secondary endpoint. Conclusions: This study suggests that LMWH might reduce the risk of in-hospital mortality and severe ARDS in coronavirus disease 2019. Randomized controlled trials are warranted to confirm these preliminary findings.

Role of Low-Molecular-Weight Heparin in Hospitalized Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia: A Prospective Observational Study

Maggi F.;
2020

Abstract

Background: This study was conducted to evaluate the impact of low-molecular-weight heparin (LMWH) on the outcome of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Methods: This is a prospective observational study including consecutive patients with laboratory-confirmed SARS-CoV-2 pneumonia admitted to the University Hospital of Pisa (March 4-April 30, 2020). Demographic, clinical, and outcome data were collected. The primary endpoint was 30-day mortality. The secondary endpoint was a composite of death or severe acute respiratory distress syndrome (ARDS). Low-molecular-weight heparin, hydroxychloroquine, doxycycline, macrolides, antiretrovirals, remdesivir, baricitinib, tocilizumab, and steroids were evaluated as treatment exposures of interest. First, a Cox regression analysis, in which treatments were introduced as time-dependent variables, was performed to evaluate the association of exposures and outcomes. Then, a time-dependent propensity score (PS) was calculated and a PS matching was performed for each treatment variable. Results: Among 315 patients with SARS-CoV-2 pneumonia, 70 (22.2%) died during hospital stay. The composite endpoint was achieved by 114 (36.2%) patients. Overall, 244 (77.5%) patients received LMWH, 238 (75.5%) received hydroxychloroquine, 201 (63.8%) received proteases inhibitors, 150 (47.6%) received doxycycline, 141 (44.8%) received steroids, 42 (13.3%) received macrolides, 40 (12.7%) received baricitinib, 13 (4.1%) received tocilizumab, and 13 (4.1%) received remdesivir. At multivariate analysis, LMWH was associated with a reduced risk of 30-day mortality (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.21-0.6; P <.001) and composite endpoint (HR, 0.61; 95% CI, 0.39-0.95; P =.029). The PS-matched cohort of 55 couples confirmed the same results for both primary and secondary endpoint. Conclusions: This study suggests that LMWH might reduce the risk of in-hospital mortality and severe ARDS in coronavirus disease 2019. Randomized controlled trials are warranted to confirm these preliminary findings.
ARDS; COVID-19; low-molecular weight; mortality; SARS-CoV-2
Falcone, M.; Tiseo, G.; Barbieri, G.; Galfo, V.; Russo, A.; Virdis, A.; Forfori, F.; Corradi, F.; Guarracino, F.; Carrozzi, L.; Celi, A.; Santini, M.; Monzani, F.; De Marco, S.; Pistello, M.; Danesi, R.; Ghiadoni, L.; Farcomeni, A.; Menichetti, F.; Sabrina, A. O. D.; Rachele, A.; Rubia, B.; Pietro, B.; Martina, B.; Matteo, B.; Giulia, B.; Valeria, C.; Nicoletta, C.; Francesco, C.; Alessandro, C.; Alessandra, D. R.; Massimiliano, D.; Giovanna, F.; Marco, G.; Maggi, F.; Alessandro, M.; Paolo, M.; Stefano, M.; Marco, M.; Alessandra, M.; Elia, N.; Naria, P.; Simone, P.; Chiara, P.; Francesca, R.; Maria, S.; Massimiliano, S.; Stefano, S.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/2131910
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