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

• DOI: 10.1055/a-1347-6070
• Publication Date: 2021-01-07T23:57:19Z
• Authors: Augusto Di Castel...; 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 Agos...; 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 Gaetan...; Francesco Di Gennaro; Giuseppe Di Tano; Gianpiero D'Offizi; Massimo Fantoni; Francesco Maria F...; 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 Si...; Eleonora Taddei; Carlo Torti; Roberto Vettor; Andrea Vianello; Marco Vinceti; Alexandra Virano; Laura Vocciante; Raffaele De Caterina; Licia Iacoviello
• Keywords: Male; coronavirus; 610; heparin; 03 medical and health sciences; 0302 clinical medicine; Humans; Thrombophilia; Hospital Mortality; Blood Coagulation; Aged; Retrospective Studies; Heparin; Anticoagulants; COVID-19; Hematology; Heparin, Low-Molecular-Weight; Middle Aged; mortality; Survival Analysis; COVID-19 Drug Treatment; 3. Good health; coronaviru; coagulation activation; coagulation activation; coronavirus; COVID-19; heparin; mortality; treatments;; Italy; treatments; covid 19, heparin; coagulation activation; coronavirus; COVID-19; heparin; mortality; treatments; Female; coagulation activation; coronavirus; COVID-19; heparin; mortality; treatments; Aged; Anticoagulants; Blood Coagulation; COVID-19; Female; Heparin; Heparin, Low-Molecular-Weight; Hospital Mortality; Humans; Italy; Male; Middle Aged; Retrospective Studies; Survival Analysis; Thrombophilia; COVID-19; coronavirus; heparin; coagulation activation; treatments; mortality

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.