Anticoagulation Before Hospitalization Is a Potential Protective Factor for COVID-19: Insight From a French Multicenter Cohort Study

Abstract

Background Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with thrombotic outcomes with coagulation and endothelial disorders. Based on that, several anticoagulation guidelines have been proposed. We aimed to determine whether anticoagulation therapy modifies the risk of developing severe COVID-19. Methods and Results Patients with COVID-19 initially admitted in medical wards of 24 French hospitals were included prospectively from February 26 to April 20, 2020. We used a Poisson regression model, Cox proportional hazard model, and matched propensity score to assess the effect of anticoagulation on outcomes (intensive care unit admission or in-hospital mortality). The study enrolled 2878 patients with COVID-19, among whom 382 (13.2%) were treated with oral anticoagulation therapy before hospitalization. After adjustment, anticoagulation therapy before hospitalization was associated with a better prognosis with an adjusted hazard ratio of 0.70 (95% CI, 0.55-0.88). Analyses performed using propensity score matching confirmed that anticoagulation therapy before hospitalization was associated with a better prognosis, with an adjusted hazard ratio of 0.43 (95% CI, 0.29-0.63) for intensive care unit admission and adjusted hazard ratio of 0.76 (95% CI, 0.61-0.98) for composite criteria intensive care unit admission or death. In contrast, therapeutic or prophylactic low- or high-dose anticoagulation started during hospitalization were not associated with any of the outcomes. Conclusions Anticoagulation therapy used before hospitalization in medical wards was associated with a better prognosis in contrast with anticoagulation initiated during hospitalization. Anticoagulation therapy introduced in early disease could better prevent COVID-19-associated coagulopathy and endotheliopathy, and lead to a better prognosis.

Keywords: COVID‐19; SARS‐CoV‐2; anticoagulant; coagulopathy; mortality.

Conflict of interest statement

Drs Chocron, Gendron, Sanchez, Cohen, and Smadja acknowledge the following without any relation to the current manuscript. Dr Chocron received consultant fees from Aspen. Dr Cohen received research grant from RESICARD (research nurses) and consultant and lecture fees from Amgen, AstraZeneca, Bayer, Alliance Bristol‐Myers Squibb/Pfizer, Novartis, and Sanofi‐Aventis. Dr Smadja received consultant and lecture fees or travel awards from Aspen, Bayer, Carmat, Alliance Bristol‐Myers Squibb/Pfizer, LEO‐Pharma, and Boehringer‐Ingelheim. Dr Sanchez received grants, personal fees, or nonfinancial support from Bayer, Alliance Bristol‐Myers Squibb/Pfizer, Sanofi Aventis, Daiichi Sankyo, MSD, Boston Scientifics, and Chiesi. Dr Gendron discloses consulting fees by Boehringer‐Ingelheim, Bayer, Alliance Bristol‐Myers Squibb/Pfizer, and LEO‐Pharma. The remaining authors have no disclosures to report.

Figures

Figure 1. Survival curves of Cox proportional hazard model according to admission to ICU admission.

A, Admission to in‐hospital mortality, or ICU admission as a composite event to define ICU‐free survival (B) and to admission to in hospital mortality (C). Cox proportional hazards model is adjusted for sex, age, cardiovascular comorbidities (history of high blood pressure. dyslipidemia. body mass index, type 2 diabetes mellitus, and current smoking), plasma creatinine level (µmol/L), C‐reactive protein (mg/L), and fraction of inspired oxygen. The degree of pulmonary lesions with ground‐glass opacities and areas of consolidation and the use of in hospital anticoagulation (preventive low or high dose and therapeutic dose anticoagulation). DOAC indicates direct oral anticoagulant; ICU, intensive care unit; and VKA, vitamin K antagonist.

Figure 2. Forest plot of Cox proportional hazard model in the entire population (n=2748), according to admission to in‐hospital mortality or ICU admission as a composite event to define ICU‐free survival.

aHR indicates adjusted hazard ratio; CT, computed tomography; DOAC, direct oral anticoagulant; FiO2, fraction of inspired oxygen; ICU, intensive care unit; and VKA, vitamin K antagonist.