Thromboprophylaxis in outpatients with Covid-19

A preventative treatment with heparin injections had no impact on hospitalisations and mortality rates among symptomatic Covid-19 outpatients.

Covid-19 is associated with an increased risk of developing arterial and venous thromboses, which worsen the course of the illness and may be fatal. In hospital, admitted patients routinely receive blood thinners with heparin for thrombosis prevention. In ambulatory patients, who represent the vast majority of subjects with COVID-19, no evidence was available until now and, therefore, it was unclear whether a routine thrombosis prevention may be effective and safe.

This was the background that led to the design of the OVID academic trial in April 2020. The study was carried out by a multinational research team led by Stefano Barco and Nils Kucher from the Department of Angiology, University Hospital Zurich. The researchers investigated whether a prophylactic administration of heparin may lead to a reduction in hospitalisation and mortality among COVID-19 patients who received an initial treatment at home.

The study was carried out in eight hospitals in Switzerland and Germany. The main inclusion criteria were age over 50 years and the presence of either respiratory symptoms or a body temperature of more than 37.5°C in association with acute Covid-19, provided the patients had to other reason for hospitalisation. The blood thinner heparin has anti-inflammatory and anti-thrombotic effects: half of subjects were randomly assigned to receive a daily dose of Enoxaparin subcutaneously, a low-molecular-weight heparin, over two weeks. The control group received the standard of care treatment, namely no anti-thrombotic medication. The study included 472 people and was carried out over 1.5 years.

As the underlying hypothesis was not proven, the trial was terminated prematurely based on the results of the first interim analysis. Within 30 days of inclusion in the study and Covid-19 diagnosis, no difference was found in the incidence of hospitalisations and mortality between the two groups. Although fewer pulmonary embolisms were observed in the group of patients treated with heparin, this correlation did not reach statistical significance also due to the relatively small sample size of the study.

The Principal Investigators of the study commented that only few individuals aged over 70 years could have been included in OVID. Therefore, these results should drive clinical decision primarily for the group of patients between 50 and 70 years, whereas further research is needed for older patients. OVID is the first and, to date, the largest study investigating heparin thromboprophylaxis in Covid-19 outpatients. The authors are currently planning a pooled analysis of OVID with a similar study (“Early thromboprophylaxis in COVID-19 ETHIC” study) from London (UK).

These findings will indeed be relevant for the preparation of future guidelines and indicate that a routine thromboprophylaxis is not required on a routine basis for the management of Covid-19 in the outpatient setting.

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