Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study.

Augusto Di Castelnuovo,Simona Costanzo,Andrea Antinori,Nausicaa Berselli,Lorenzo Blandi,Marialaura Bonaccio,Roberto Cauda,Giovanni Guaraldi,Lorenzo Menicanti,Marco Mennuni,Giustino Parruti,Giuseppe Patti,Francesca Santilli,Carlo Signorelli,Alessandra Vergori,Pasquale Abete,Walter Ageno,Antonella Agodi,Piergiuseppe Agostoni,Luca Aiello,Samir Al Moghazi,Rosa Arboretti,Marinella Astuto,Filippo Aucella,Greta Barbieri,Alessandro Bartoloni,Paolo Bonfanti,Francesco Cacciatore,Lucia Caiano,Laura Carrozzi,Antonio Cascio,Arturo Ciccullo,Antonella Cingolani,Francesco Cipollone,Claudia Colomba,Crizia Colombo,Francesca Crosta,Gian Battista Danzi,Damiano D'Ardes,Katleen de Gaetano Donati,Francesco Di Gennaro,Giuseppe Di Tano,Gianpiero D'Offizi,Massimo Fantoni,Francesco Maria Fusco,Ivan Gentile,Francesco Gianfagna,Elvira Grandone,Emauele Graziani,Leonardo Grisafi,Gabriella Guarnieri,Giovanni Larizza,Armando Leone,Gloria Maccagni,Ferruccio Madaro,Stefano Maitan,Sandro Mancarella,Massimo Mapelli,Riccardo Maragna,Rossella Marcucci,Giulio Maresca,Silvia Marongiu,Claudia Marotta,Lorenzo Marra,Franco Mastroianni,Maria Mazzitelli,Alessandro Mengozzi,Francesco Menichetti,Marianna Meschiari,Jovana Milic,Filippo Minutolo,Beatrice Molena,Arturo Montineri,Cristina Mussini,Maria Musso, Daniela Niola,Anna Odone,Marco Olivieri,Antonella Palimodde,Roberta Parisi,Emanuela Pasi,Raffaele Pesavento,Francesco Petri,Biagio Pinchera,Venerino Poletti,Claudia Ravaglia,Andrea Rognoni,Marco Rossato,Marianna Rossi,Vincenzo Sangiovanni,Carlo Sanrocco,Laura Scorzolini,Raffaella Sgariglia,Paola Giustina Simeone,Eleonora Taddei,Carlo Torti,Roberto Vettor,Andrea Vianello,Marco Vinceti,Alexandra Virano,Laura Vocciante,Raffaele De Caterina,Licia Iacoviello

Thrombosis and haemostasis(2021)

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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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