Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: the Multicenter Italian CORIST Study[*]Funding None.
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.
Prof. Iacoviello and Di Castelnuovo had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Di Castelnuovo, Costanzo, Iacoviello, and De Caterina. Acquisition, analysis, or interpretation of data: all authors. Drafting of the manuscript: Iacoviello, Di Castelnuovo and Costanzo. Critical revision of the manuscript for important intellectual content: Iacoviello, Di Castelnuovo, De Caterina, and de Gaetano Donati. Statistical analysis: Costanzo, Di Castelnuovo, and Arboretti. Administrative, technical, or material support: all authors. Supervision: Iacoviello and Di Castelnuovo.
* THE COVID-19 RISK and Treatments (CORIST) collaboration.
** These authors contributed equally to this work.
Received: 14 December 2020
Accepted: 06 January 2021
07 January 2021 (online)
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
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