Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study
Authors: 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 
Published: January 2021

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.