Augusto Di Castelnuovo1, Simona Costanzo2, Andrea Antinori3, Nausicaa Berselli4, Lorenzo Blandi5, Marialaura Bonaccio2, Roberto Cauda6,7, Giovanni Guaraldi8, Lorenzo Menicanti9, Marco Mennuni10, Giustino Parruti11, Giuseppe Patti10, Francesca Santilli12, Carlo Signorelli13, Alessandra Vergori14, Pasquale Abete15, Walter Ageno16, Antonella Agodi17, Piergiuseppe Agostoni18,19, Luca Aiello20, Samir Al Moghazi21, Rosa Arboretti22, Marinella Astuto23, Filippo Aucella24, Greta Barbieri25, Alessandro Bartoloni26, Paolo Bonfanti27,28, Francesco Cacciatore15, Lucia Caiano16, Laura Carrozzi29, Antonio Cascio30, Arturo Ciccullo6, Antonella Cingolani6,7, Francesco Cipollone12, Claudia Colomba30, Crizia Colombo10, Francesca Crosta11, Gian Battista Danzi31, Damiano D'Ardes12, Katleen de Gaetano Donati6, Francesco Di Gennaro32, Giuseppe Di Tano31, Gianpiero D'Offizi33, Massimo Fantoni6,7, Francesco Maria Fusco34, Ivan Gentile35, Francesco Gianfagna1,16, Elvira Grandone24, Emauele Graziani36, Leonardo Grisafi10, Gabriella Guarnieri37, Giovanni Larizza38, Armando Leone39, Gloria Maccagni31, Ferruccio Madaro38, Stefano Maitan20, Sandro Mancarella40, Massimo Mapelli18,19, Riccardo Maragna18,19, Rossella Marcucci26, Giulio Maresca41, Silvia Marongiu42, Claudia Marotta32, Lorenzo Marra39, Franco Mastroianni38, Maria Mazzitelli43, Alessandro Mengozzi44, Francesco Menichetti44, Marianna Meschiari8, Jovana Milic8, Filippo Minutolo45, Beatrice Molena37, Arturo Montineri46, Cristina Mussini8, Maria Musso47, Daniela Niola12, Anna Odone5, Marco Olivieri48, Antonella Palimodde42, Roberta Parisi2, Emanuela Pasi36, Raffaele Pesavento49, Francesco Petri27, Biagio Pinchera35, Venerino Poletti50,51, Claudia Ravaglia50, Andrea Rognoni10, Marco Rossato49, Marianna Rossi27, Vincenzo Sangiovanni34, Carlo Sanrocco11, Laura Scorzolini52, Raffaella Sgariglia40, Paola Giustina Simeone11, Eleonora Taddei6, Carlo Torti43, Roberto Vettor49, Andrea Vianello37, Marco Vinceti4,53, Alexandra Virano16, Laura Vocciante41, Raffaele De Caterina29, Licia Iacoviello2,16. 1. Mediterranea Cardiocentro, Napoli, Italy. 2. Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy. 3. UOC Immunodeficienze Virali, National Institute for Infectious Diseases "L. Spallanzani," IRCCS, Rome, Italy. 4. Section of Public Health, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy. 5. Università di Pavia, Pavia, Italy. 6. Fondazione Policlinico Universitario A, Gemelli IRCCS, Rome, Italy. 7. Dipartimento di Sicurezza e Bioetica Sede di Roma, Università Cattolica del Sacro Cuore, Rome, Italy. 8. Infectious Disease Unit, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy. 9. IRCCS Policlinico San Donato, San Donato, Milanese (MI), Italy. 10. University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy. 11. Department of Infectious Disease, Azienda Sanitaria Locale (AUSL) di Pescara, Pescara, Italy. 12. Department of Medicine and Aging, Clinica Medica, "SS. Annunziata" Hospital and University of Chieti, Chieti, Italy. 13. School of Medicine, Vita-Salute San Raffaele University, Milan, Italy. 14. Department of HIV/AIDS, National Institute for Infectious Diseases "Lazzaro Spallanzani"-IRCCS, Rome, Italy. 15. Dipartimento di Scienze Mediche Traslazionali, Università degli studi di Napoli "Federico II," Napoli, Italy. 16. Department of Medicine and Surgery, University of Insubria, Varese, Italy. 17. Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia," University of Catania; AOU Policlinico "G. Rodolico - San Marco," Catania, Italy. 18. Centro Cardiologico Monzino IRCCS, Milan, Italy. 19. Section of Cardiovascular, Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy. 20. UOC, Anestesia e Rianimazione, Dipartimento di Chirurgia Generale Ospedale Morgagni-Pierantoni, Forlì, Italy. 21. UOC Infezioni Sistemiche dell'Immunodepresso, National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy. 22. Department of Civil Environmental and Architectural Engineering, University of Padova, Padova, Italy. 23. Department of General Surgery and Medical-Surgical Specialties, University of Catania, U.O. Anestesia, Rianimazione 1. P.O. "G. Rodolico," AOU Policlinico "G. Rodolico - San Marco," Catania, Italy. 24. Fondazione I.R.C.C.S "Casa Sollievo della Sofferenza," San Giovanni Rotondo, Foggia, Italy. 25. Department of Surgical, Medical and Molecular Medicine and Critical Care, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Pisa, Italy. 26. Department of Experimental and Clinical Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy. 27. UOC Malattie Infettive, Ospedale San Gerardo, ASST Monza, Monza, Italy. 28. School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy. 29. Cardiovascular and Thoracic Department, Azienda Ospedaliero-Universitaria Pisana and University of Pisa, Pisa, Italy. 30. Infectious and Tropical Diseases Unit, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy. 31. Department of Cardiology, Ospedale di Cremona, Cremona, Italy. 32. Medical Direction, IRCCS Neuromed, Pozzilli, Isernia, Italy. 33. UOC Malattie Infettive-Epatologia, National Institute for Infectious Diseases L, Spallanzani, IRCCS, Roma, Italy. 34. UOC Infezioni Sistemiche e dell'Immunodepresso, Azienda Ospedaliera dei Colli, Ospedale Cotugno, Napoli, Italy. 35. Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy. 36. Medicina Interna, Ospedale di Ravenna, AUSL della Romagna, Ravenna, Italy. 37. Division of Respiratory Pathophysiology, Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy. 38. COVID-19 Unit, EE Ospedale Regionale F. Miulli, Acquaviva delle Fonti, Bari, Italy. 39. UOC di Pneumologia, P.O. San Giuseppe Moscati, Taranto, Italy. 40. ASST Milano Nord, Ospedale Edoardo Bassini Cinisello Balsamo, Milan, Italy. 41. UOC di Medicina - Presidio Ospedaliero S. Maria di Loreto Nuovo. ASL Napoli 1 Centro. Napoli. Italy. 42. P.O. Santissima Trinità di Cagliari, Cagliari, Italy. 43. Infectious and Tropical Diseases Unit, Department of Medical and Surgical Sciences "Magna Graecia" University, Catanzaro, Italy. 44. Department of Clinical and Experimental Medicine, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Pisa, Italy. 45. Dipartimento di Farmacia, Università di Pisa, Pisa, Italy. 46. U.O. C. Malattie Infettive e Tropicali, P.O. "San Marco." AOU Policlinico "G. Rodolico - San Marco," Catania, Italy. 47. UOC Malattie Infettive-Apparato Respiratorio, National Institute for Infectious Diseases "L. Spallanzani," IRCCS, Rome, Italy. 48. Computer Service, University of Molise, Campobasso, Italy. 49. Clinica Medica 3, Department of Medicine - DIMED, University hospital of Padova, Padova, Italy. 50. UOC Pneumologia, Dipartimento di Malattie Apparato Respiratorio e Torace, Ospedale Morgagni-Pierantoni, Forlì, Italy. 51. Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark. 52. UOC Malattie Infettive ad Alta Intensità di Cura, National Institute for Infectious Diseases "L. Spallanzani," IRCCS, Rome, Italy. 53. Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States.
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. Thieme. All rights reserved.
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. Thieme. All rights reserved.
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Authors: B Pinchera; R Scotto; A R Buonomo; E Zappulo; F Stagnaro; A Gallicchio; G Viceconte; A Sardanelli; S Mercinelli; R Villari; M Foggia; I Gentile Journal: Diabetes Res Clin Pract Date: 2022-03-03 Impact factor: 8.180