Patients given prophylactic anticoagulants within 24 hours of admission to hospital with COVID-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events, found a UK/US research team. This is "strong real world evidence" to support guidelines recommending blood thinners as initial treatment for COVID patients with upon admission, the authors say.
The study was conducted by researchers at the London School of Hygiene & Tropical Medicine, VA Connecticut Healthcare System, Vanderbilt University Medical Centre and Vanderbilt Translational and Clinical Cardiovascular Research Centre, University of Pittsburgh, Veterans Affairs Pittsburgh Healthcare System, Yale School of Medicine, Massachusetts Veterans Epidemiology Research and Information Centre (MAVERIC), Vanderbilt University School of Medicine, Rocky Mountain Regional VA Medical Centre, VA Palo Alto Healthcare System, Stanford University School of Medicine, Oak Ridge National Laboratory, Yale School of Public Health and the Tennessee Valley Healthcare System.
Clinical trials are now underway to see if prophylactic anticoagulants could be an effective treatment for COVID-19. In the meantime, the researchers say these findings provide strong real-world evidence to support their early use among patients in hospital with COVID-19.
Some COVID deaths are believed to be due to blood clots developing in major veins and arteries. Anticoagulants prevent blood clots forming and have antiviral and potentially anti-inflammatory properties, so might be particularly effective in patients with COVID-19, but results from previous studies have been inconclusive.
To explore this further, a team of UK and US researchers set out to estimate the effect of prophylactic anticoagulants when given promptly after admission to hospital on risk of death and severe bleeding among patients with COVID-19.
Their findings are based on data from the US Department of Veterans Affairs for 4,297 patients (average age 68 years; 93% men) admitted to hospital with covid-19 between 1 March and 31 July 2020.
Other potentially important factors including age, ethnicity, underlying conditions, medication history, weight, and smoking status were taken into account. The researchers then followed these patients to see who died or experienced a serious bleeding event within 30 days of hospital admission.
A total of 3,627 (84.4%) of patients received prophylactic anticoagulation within 24 hours of admission and there were 622 deaths (14.5%) within 30 days.
Death at 30 days was 14.3% among those who received prophylactic anticoagulation compared with 18.7% among those who did not – a relative risk reduction as high as 34% and an absolute risk reduction of 4.4%.
This benefit seemed to be greater among patients not admitted to the intensive care unit (ICU) within 24 hours of hospital admission.
Receiving prophylactic anticoagulation was not associated with an increased risk of serious bleeding.
This was a large, well-designed study using electronic health record data and took account of a range of potentially influential factors. Results were also unchanged after further analyses, suggesting that they withstand scrutiny.
However, the researchers acknowledge that due to the observational nature of the study, a degree of uncertainty persists that can only be addressed through randomised trials.
Until further trial evidence is available, they conclude that these findings "provide strong real-world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with COVID-19 on hospital admission."
Study details
Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study
Christopher T Rentsch, Joshua A Beckman, Laurie Tomlinson, Walid F Gellad, Charles Alcorn, Farah Kidwai-Khan, Melissa Skanderson, Evan Brittain, Joseph T King, Yuk-Lam Ho, Svetlana Eden, Suman Kundu, Michael F Lann, Robert A Greevy, P Michael Ho, Paul A Heidenreich, Daniel A Jacobson, Ian J Douglas, Janet P Tate, Stephen J W Evans, David Atkins, Amy C Justice, Matthew S Freiberg
Published in BMJ on 1 February 2021
Abstract
Objective
To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States.
Design
Observational cohort study.
Setting
Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system.
Participants
All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation.
Main outcome measures
The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion.
Results
Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses.
Conclusions
Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.
[link url="https://www.bmj.com/company/newsroom/preventive-blood-thinning-drugs-linked-to-reduced-risk-of-death-in-covid-19-patients/"]BMJ material[/link]
[link url="https://www.bmj.com/content/372/bmj.n311"]BMJ study (Open access)[/link]