Prophylactic Anticoagulation for Patients Hospitalized with COVID-19 Reduces Mortality
Takeaway: New research in The British Medical Journal (BMJ) provides strong real-world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial therapy for COVID-19 patients upon hospital admission.
Deaths among individuals with COVID-19 have been partially attributed to venus thromboembolism (deep vein thrombosis) and arterial thromboses (blood clot in the arteries). In response, several expert organizations recommend using prophylactic anticoagulation for patients admitted with COVID-19, who do not have a contraindication to this therapy. While evaluations of the efficacy of prophylactic anticoagulation in patients with COVID-19 in randomized clinical trials are underway, they have not yet been reported. Further, previous observational studies have been limited in sample size or used relatively small healthcare systems.
"Previous research using real-world data has not comprehensively accounted for all the reasons why people are given, or not given, anticoagulation. We designed our study to emulate a clinical trial around the specific question of whether prophylactic doses of anticoagulation given at the time of hospital admission prevented deaths from COVID-19 in patients who were eligible to receive it." Christopher Rentsch, PhD, MPH, Co-lead author*.
This observational study sought to determine whether early initiation of prophylactic anticoagulation compared to no anticoagulation decreased risk of death in patients hospitalized with COVID-19. Using VA data, investigators included all Veterans hospitalized between March 1 and July 31, 2020, who were confirmed to have COVID-19 on or within 14 days of hospital admission. The final cohort included 4,297 Veterans; 3,627 (84%) of whom received prophylactic anticoagulation within 24 hours of hospital admission. The main outcome measure was 30-day mortality. Findings show:
- After accounting for a large number of demographic and clinical characteristics, mortality at 30 days was 14.3% among Veterans who received prophylactic anticoagulation and 18.7% among patients who did not, resulting in a 27% decreased risk for 30-day mortality. This benefit appeared to be greater among patients not transferred to the ICU within 24 hours of admission.
- Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation.
- In a post-hoc safety analysis, the receipt of prophylactic anticoagulation was not associated with an increased risk of bleeding that required a transfusion.
- Results were unchanged in several sensitivity 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 randomized trials.
Turning Research Findings into Practice
Investigators have reported these findings to VA Central Office, Washington, DC, and Chief Medical Officers who have taken steps to implement these findings into VA clinical care. They also have made several presentations, including one to the VA-DOE, HHS COVID-19 Insights Partnership – an initiative to coordinate and share health data, as well as research and expertise to aid in the fight against COVID-19. In addition, the findings have been published in The BMJ, prompting several press releases.
“We believe the evidence is becoming clear that initiating prophylactic anticoagulation in earlier stages of severe COVID-19 provides greater benefit than initiating prophylactic or full-dose anticoagulation when critically ill. We eagerly await the full reporting of ongoing clinical trials, particularly those investigating whether this therapy should be given to non-hospitalized people newly diagnosed with COVID-19.” - Christopher Rentsch
About the Investigators
Christopher Rentsch, PhD, MPH
Funded by VA/HSR&D and the National Institutes of Health (NIH), this study was conducted by several HSR&D investigators, including co-lead author Christopher Rentsch, PhD, who is part of part of HSR&D’s Pain Research, Informatics, Multi-morbidities, and Education (PRIME) Center in West Haven, CT. Dr. Rentsch is an epidemiologist specializing in the use of electronic health records (EHRs), with a focus on creating real-world evidence for the safety and effectiveness of medications. He is an active member of EHR Research Groups at VA and the London School of Hygiene & Tropical Medicine (LSHTM). During the coronavirus pandemic, his research has focused on investigating potential pharmacotherapies for the prevention and treatment of COVID-19, identifying racial and ethnic disparities in COVID-19 from testing to mortality, and quantifying excess risks for long-term outcomes among COVID-19 survivors.
Other HSR&D researchers on this study include: Drs. Joseph King Jr., Janet Tate, and Amy Justice are part of HSR&D’s Pain Research, Informatics, Multi-morbidities, and Education (PRIME) Center in West Haven, CT. Dr. Walid Gellad is with HSR&D’s Center for Health Equity, Research and Promotion (CHERP) in Pittsburgh and Philadelphia, PA. Dr. Paul Heidenreich is with HSR&D’s Center for Innovation to Implementation (Ci2i) in Palo Alto, CA. Dr. David Atkins is Director of HSR&D in Washington, DC. And Dr. Matthew Freiberg is part of the Tennessee Valley Healthcare System.
*Rentsch C, Beckman J, Tomlinson L, Gellad W, Alcorn C, Kidwai-Kahn F, Skanderson M, Brittain E, King Jr. J, Ho Y-L, Eden S, Kundu S, Lann M, Greevy Jr. R, Ho PM, Heidenreich P, Jacobson D, Douglas I, Tate J, Evans S, Atkins D, Justice A, and Freiberg M. Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: Cohort study. The British Medical Journal. February 11, 2021. DOI: 10.1136/bmj.n311