Pre-medication with oral anticoagulants is associated with better outcomes in a large multinational COVID-19 cohort with cardiovascular comorbidities

Abstract

Aims: Coagulopathy and venous thromboembolism are common findings in coronavirus disease 2019 (COVID-19) and are associated with poor outcome. Timely initiation of anticoagulation after hospital admission was shown to be beneficial. In this study we aim to examine the association of pre-existing oral anticoagulation (OAC) with outcome among a cohort of SARS-CoV-2 infected patients.

Methods and results: We analysed the data from the large multi-national Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) from March to August 2020. Patients with SARS-CoV-2 infection were eligible for inclusion. We retrospectively analysed the association of pre-existing OAC with all-cause mortality. Secondary outcome measures included COVID-19-related mortality, recovery and composite endpoints combining death and/or thrombotic event and death and/or bleeding event. We restricted bleeding events to intracerebral bleeding in this analysis to ensure clinical relevance and to limit reporting errors. A total of 1 433 SARS-CoV-2 infected patients were analysed, while 334 patients (23.3%) had an existing premedication with OAC and 1 099 patients (79.7%) had no OAC. After risk adjustment for comorbidities, pre-existing OAC showed a protective influence on the endpoint death (OR 0.62, P = 0.013) as well as the secondary endpoints COVID-19-related death (OR 0.64, P = 0.023) and non-recovery (OR 0.66, P = 0.014). The combined endpoint death or thrombotic event tended to be less frequent in patients on OAC (OR 0.71, P = 0.056).

Conclusions: Pre-existing OAC is protective in COVID-19, irrespective of anticoagulation regime during hospital stay and independent of the stage and course of disease.

Keywords: COVID-19; Oral anticoagulation; SARS-CoV-2; Thrombosis.

Fig. 1

Definition of the different phases (uncomplicated, complicated and critical) of COVID-19 disease used for this analysis

Fig. 2

Schematic representation of the allocation to the cohort with or without pre-existing oral anticoagulation. Of the 3165 patients initially included in this analysis, we had to exclude 1643 patients due to missing information on oral anticoagulation or atrial fibrillation as a relevant comorbidity. Furthermore, all patients with retrospective COVID-19 diagnosis post mortem were excluded. Finally, 334 patients with pre-existing OAC and 1099 patients without pre-existing oral anticoagulation were included in the analysis. The flow diagram is based on the STROBE criteria for reporting of observational studies [38, 39]

Fig. 3

Risk-adjusted outcomes in patients pre-treated with oral anticoagulation and in a cohort without oral anticoagulation pre-treatment. The results of multivariate logistic regression analyses with 23 predefined baseline patient characteristics included as potential confounders (all covariates listed in Table 3)