1. Heparin in COVID-19 patients is associated with reduced in-hospital mortality: the multicentre Italian CORIST Study
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Walter Ageno, Raffaele Pesavento, Marinella Astuto, Katleen de Gaetano Donati, Francesca Santilli, Filippo Aucella, Eleonora Taddei, Marianna Meschiari, Laura Scorzolini, Biagio Pinchera, Giustino Parruti, Licia Iacoviello, Andrea Vianello, Gabriella Guarnieri, Arturo Montineri, Crizia Colombo, Carlo Signorelli, Lorenzo Blandi, Raffaele De Caterina, Maria Musso, Francesco Petri, Stefano Maitan, Anna Odone, Lucia Caiano, Francesca Crosta, Lorenzo Marra, Giuseppe Patti, Emanuela Pasi, Jovana Milic, Marco Olivieri, Claudia Colomba, Francesco Maria Fusco, Claudia Ravaglia, Alexandra Virano, Carlo Torti, Samir Al Moghazi, Venerino Poletti, Riccardo Maragna, Carlo Sanrocco, Sandro Mancarella, Greta Barbieri, Arturo Ciccullo, Leonardo Grisafi, Paola Simeone, Lorenzo Menicanti, Antonella Palimodde, Gloria Maccagni, Alessandra Vergori, Daniela Niola, Marco G. Mennuni, Gianpiero D'Offizi, Claudia Marotta, Damiano D'Ardes, Vincenzo Sangiovanni, Paolo Bonfanti, Giovanni Larizza, Francesco Di Gennaro, Alessandro Mengozzi, Massimo Mapelli, Giuseppe Di Tano, Laura Carrozzi, Antonella Agodi, Francesco Menichetti, Marialaura Bonaccio, Andrea Antinori, Marco Vinceti, Armando Leone, Franco Mastroianni, Silvia Marongiu, Filippo Minutolo, Giulio Maresca, Beatrice Molena, Nausicaa Berselli, Francesco Cipollone, Massimo Fantoni, Antonella Cingolani, Giovanni Guaraldi, Raffaella Sgariglia, Piergiuseppe Agostoni, Antonio Cascio, Maria Mazzitelli, Roberta Parisi, Augusto Di Castelnuovo, Gian Battista Danzi, Luca Aiello, Roberto Vettor, Elvira Grandone, Laura Vocciante, Emauele Graziani, Cristina Mussini, Marianna Rossi, Marco Rossato, Roberto Cauda, Rosa Arboretti, Alessandro Bartoloni, Simona Costanzo, Francesco Gianfagna, Andrea Rognoni, Ferruccio Madaro, Rossella Marcucci, Pasquale Abete, Francesco Cacciatore, Ivan Gentile, Di Castelnuovo, A, Costanzo, S, Antinori, A, Berselli, N, Blandi, L, Bonaccio, M, Cauda, R, Guaraldi, G, Menicanti, L, Mennuni, M, Parruti, G, Patti, G, Santilli, F, Signorelli, C, Vergori, A, Abete, P, Ageno, W, Agodi, A, Agostoni, P, Aiello, L, Al Moghazi, S, Arboretti, R, Astuto, M, Aucella, F, Barbieri, G, Bartoloni, A, Bonfanti, P, Cacciatore, F, Caiano, L, Carrozzi, L, Cascio, A, Ciccullo, A, Cingolani, A, Cipollone, F, Colomba, C, Colombo, C, Crosta, F, Danzi, G, D'Ardes, D, de Gaetano Donati, K, Di Gennaro, F, Di Tano, G, D'Offizi, G, Fantoni, M, Fusco, F, Gentile, I, Gianfagna, F, Grandone, E, Graziani, E, Grisafi, L, Guarnieri, G, Larizza, G, Leone, A, Maccagni, G, Madaro, F, Maitan, S, Mancarella, S, Mapelli, M, Maragna, R, Marcucci, R, Maresca, G, Marongiu, S, Marotta, C, Marra, L, Mastroianni, F, Mazzitelli, M, Mengozzi, A, Menichetti, F, Meschiari, M, Milic, J, Minutolo, F, Molena, B, Montineri, A, Mussini, C, Musso, M, Niola, D, Odone, A, Olivieri, M, Palimodde, A, Parisi, R, Pasi, E, Pesavento, R, Petri, F, Pinchera, B, Poletti, V, Ravaglia, C, Rognoni, A, Rossato, M, Rossi, M, Sangiovanni, V, Sanrocco, C, Scorzolini, L, Sgariglia, R, Simeone, P, Taddei, E, Torti, C, Vettor, R, Vianello, A, Vinceti, M, Virano, A, Vocciante, L, De Caterina, R, Iacoviello, L, Danzi, G. B, De Gaetano Donati, K, Fusco, F. M, Simeone, P. G, Iacoviello, L., Di Castelnuovo, Augusto, Costanzo, Simona, Antinori, Andrea, Berselli, Nausicaa, Blandi, Lorenzo, Bonaccio, Marialaura, Cauda, Roberto, Guaraldi, Giovanni, Menicanti, Lorenzo, Mennuni, Marco, Parruti, Giustino, Patti, Giuseppe, Santilli, Francesca, Signorelli, Carlo, Vergori, Alessandra, Abete, Pasquale, Ageno, Walter, Agodi, Antonella, Agostoni, Piergiuseppe, Aiello, Luca, Al Moghazi, Samir, Arboretti, Rosa, Astuto, Marinella, Aucella, Filippo, Barbieri, Greta, Bartoloni, Alessandro, Bonfanti, Paolo, Cacciatore, Francesco, Caiano, Lucia, Carrozzi, Laura, Cascio, Antonio, Ciccullo, Arturo, Cingolani, Antonella, Cipollone, Francesco, Colomba, Claudia, Colombo, Crizia, Crosta, Francesca, Danzi, Gian Battista, D'Ardes, Damiano, de Gaetano Donati, Katleen, Di Gennaro, Francesco, Di Tano, Giuseppe, D'Offizi, Gianpiero, Fantoni, Massimo, Fusco, Francesco Maria, Gentile, Ivan, Gianfagna, Francesco, Grandone, Elvira, Graziani, Emauele, Grisafi, Leonardo, Guarnieri, Gabriella, Larizza, Giovanni, Leone, Armando, Maccagni, Gloria, Madaro, Ferruccio, Maitan, Stefano, Mancarella, Sandro, Mapelli, Massimo, Maragna, Riccardo, Marcucci, Rossella, Maresca, Giulio, Marongiu, Silvia, Marotta, Claudia, Marra, Lorenzo, Mastroianni, Franco, Mazzitelli, Maria, Mengozzi, Alessandro, Menichetti, Francesco, Meschiari, Marianna, Milic, Jovana, Minutolo, Filippo, Molena, Beatrice, Montineri, Arturo, Mussini, Cristina, Musso, Maria, Niola, Daniela, Odone, Anna, Olivieri, Marco, Palimodde, Antonella, Parisi, Roberta, Pasi, Emanuela, Pesavento, Raffaele, Petri, Francesco, Pinchera, Biagio, Poletti, Venerino, Ravaglia, Claudia, Rognoni, Andrea, Rossato, Marco, Rossi, Marianna, Sangiovanni, Vincenzo, Sanrocco, Carlo, Scorzolini, Laura, Sgariglia, Raffaella, Simeone, Paola Giustina, Taddei, Eleonora, Torti, Carlo, Vettor, Roberto, Vianello, Andrea, Vinceti, Marco, Virano, Alexandra, Vocciante, Laura, De Caterina, Raffaele, Iacoviello, Licia, Di Castelnuovo A., Costanzo S., Antinori A., Berselli N., Blandi L., Bonaccio M., Cauda R., Guaraldi G., Menicanti L., Mennuni M., Parruti G., Patti G., Santilli F., Signorelli C., Vergori A., Abete P., Ageno W., Agodi A., Agostoni P., Aiello L., Al Moghazi S., Arboretti R., Astuto M., Aucella F., Barbieri G., Bartoloni A., Bonfanti P., Cacciatore F., Caiano L., Carrozzi L., Cascio A., Ciccullo A., Cingolani A., Cipollone F., Colomba C., Colombo C., Crosta F., Danzi G.B., D'Ardes D., De Gaetano Donati K., Di Gennaro F., Di Tano G., D'Offizi G., Fantoni M., Fusco F.M., Gentile I., Gianfagna F., Grandone E., Graziani E., Grisafi L., Guarnieri G., Larizza G., Leone A., MacCagni G., Madaro F., Maitan S., Mancarella S., Mapelli M., Maragna R., Marcucci R., Maresca G., Marongiu S., Marotta C., Marra L., Mastroianni F., Mazzitelli M., Mengozzi A., Menichetti F., Meschiari M., Milic J., Minutolo F., Molena B., Montineri A., Mussini C., Musso M., Niola D., Odone A., Olivieri M., Palimodde A., Parisi R., Pasi E., Pesavento R., Petri F., Pinchera B., Poletti V., Ravaglia C., Rognoni A., Rossato M., Rossi M., Sangiovanni V., Sanrocco C., Scorzolini L., Sgariglia R., Simeone P.G., Taddei E., Torti C., Vettor R., Vianello A., Vinceti M., Virano A., Vocciante L., De Caterina R., and Iacoviello L.
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Male ,medicine.medical_specialty ,Settore MED/17 - Malattie Infettive ,coronavirus ,heparin ,030204 cardiovascular system & hematology ,Lower risk ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Clinical endpoint ,medicine ,Humans ,Thrombophilia ,030212 general & internal medicine ,Hospital Mortality ,Blood Coagulation ,Survival analysis ,Aged ,Retrospective Studies ,treatment ,business.industry ,Heparin ,Mortality rate ,COVID-19,mortality ,Low-Molecular-Weight ,Anticoagulants ,COVID-19 ,Retrospective cohort study ,Hematology ,Heparin, Low-Molecular-Weight ,Middle Aged ,mortality ,Survival Analysis ,COVID-19 Drug Treatment ,coagulation activation ,coronaviru ,Italy ,treatments ,Propensity score matching ,Female ,business ,medicine.drug - Abstract
Introduction A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. Aim We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. Methods In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. Results Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49–0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. Conclusion In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.
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- 2021