Role of Low-Molecular-Weight Heparin in Hospitalized Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia: A Prospective Observational Study
MD Marco Falcone, Giusy Tiseo, Greta Barbieri, Valentina Galfo, Alessandro Russo, Agostino Virdis, Francesco Forfori, Francesco Corradi, Fabio Guarracino, Laura Carrozzi, Alessandro Celi, Massimo Santini, Fabio Monzani, Salvatore De Marco, Mauro Pistello, Romano Danesi, Lorenzo Ghiadoni, Alessio Farcomeni, Francesco Menichetti, Agostini O Degl’innocenti Sabrina, Antognoli Rachele, Baldassarri Rubia, Bertini Pietro, Biancalana Martina, Borselli Matteo, Brizzi Giulia, Calsolario Valeria, Carpene Nicoletta, Cinotti Francesco, Cipriano Alessandro, Della Rocca Alessandra, Desideri Massimiliano, Forotti Giovanna, Gherardi Marco, Maggi Fabrizio, Mengozzi Alessandro, Malacarne Paolo, Masi Stefano, Monfroni Marco, Morea Alessandra, Nencini Elia, Park Naria, Paterni Simone, Piagnani Chiara, Ruberti Francesca, Sciuto Maria, Serradori Massimiliano, Spinelli Stefano
Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa563
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.
Supplementary Data Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.
APPENDIX
PISA COVID-19 Study Group Agostini o Degl'Innocenti Sabrina 1 , Antognoli Rachele 2 , Baldassarri Rubia 3 , Bertini Pietro 3 , Biancalana Martina 1 , Borselli Matteo 1 , Brizzi Giulia
References
Cangemi, Casciaro, Rossi, SIXTUS Study Group; SIXTUS Study Group. Platelet activation is associated with myocardial infarction in patients with pneumonia, J Am Coll Cardiol
Charlson, Pompei, Ales, Mackenzie, A new method of classifying prognostic comorbidity in longitudinal studies: development and validation, J Chronic Dis
Collins, Manach, Comparing treatment effects between propensity scores and randomized controlled trials: improving conduct and reporting, Eur Heart J
Du, Liang, Yang, Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study, Eur Respir J
Falcone, Russo, Cangemi, Lower mortality rate in elderly patients with community-onset pneumonia on treatment with aspirin, J Am Heart Assoc
Fox, Akmatbekov, Harbert, Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans, Lancet Respir Med
Horby, Lim, Emberson, Collaborative Group. Dexamethasone in hospitalized patients with covid-19-preliminary report, N Engl J Med
Ji, Zhang, Xu, Prediction for progression risk in patients with COVID-19 pneumonia: the CALL score, Clin Infect Dis
Lu, Propensity score matching with time-dependent covariates, Biometrics
Minuz, Mansueto, Mazzaferri, High rate of pulmonary thromboembolism in patients with SARS-CoV-2 pneumonia, Clin Microbiol Infect
Mortus, Manek, Brubaker, Thromboelastographic results and hypercoagulability syndrome in patients with coronavirus disease 2019 who are critically ill, JAMA Netw Open
Paranjpe, Fuster, Lala, Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19, J Am Coll Cardiol
Ranieri, Rubenfeld, Thompson, ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin definition, JAMA
Richardson, Hirsch, Narasimhan, the Northwell COVID-19 Research Consortium. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area, JAMA
Ruan, Yang, Wang, Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China, Intensive Care Med
Sanders, Monogue, Jodlowski, Cutrell, Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review, JAMA
Schulman, Kearon, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients, J Thromb Haemost
Smythe, Priziola, Dobesh, Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism, J Thromb Thrombolysis
Tang, Bai, Chen, Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy, J Thromb Haemost
Thachil, Juffermans, Ranucci, ISTH DIC subcommittee communication on anticoagulation in COVID-19, J Thromb Haemost
Vincent, Moreno, Takala, The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine, Intensive Care Med
Violi, Cangemi, Falcone, SIXTUS (Thrombosis-Related Extrapulmonary Outcomes in Pneumonia) Study Group. Cardiovascular complications and short-term mortality risk in community-acquired pneumonia, Clin Infect Dis
Wang, Hu, Hu, Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China, JAMA
