nference

Healthcare disparities among anticoagulation therapies for severe COVID-19 patients in the multi-site VIRUS registry

Abstract: COVID-19 patients are at an increased risk of thrombosis and various anticoagulants are being used in patient management without an established standard-of-care. Here, we analyze hospitalized and ICU patient outcomes from the Viral Infection and Respiratory illness Universal Study (VIRUS) registry. We find that severe COVID patients administered unfractionated heparin but not enoxaparin have a higher mortality-rate (311 deceased patients out of 760 total patients = 41%) compared to patients administered enoxaparin but not unfractionated heparin (214 deceased patients out of 1,432 total patients = 15%), presenting a risk ratio of 2.74 (95% C.I.: [2.35, 3.18]; p-value: 1.4e-41). This difference persists even after balancing on a number of covariates including: demographics, comorbidities, admission diagnoses, and method of oxygenation, with an amplified mortality rate of 39% (215 of 555) for unfractionated heparin vs. 23% (119 of 522) for enoxaparin, presenting a risk ratio of 1.70 (95% C.I.: [1.40, 2.05]; p-value: 2.5e-7). In these balanced cohorts, a number of complications occurred at an elevated rate for patients administered unfractionated heparin compared to those administered enoxaparin, including acute kidney injury (227 of 642 [35%] vs. 156 of 608 [26%] respectively, adjusted p-value 0.0019), acute cardiac injury (40 of 642 [6.2%] vs. 15 of 608 [2.5%] respectively, adjusted p-value 0.01), septic shock (118 of 642 [18%] vs. 73 of 608 [12%] respectively, adjusted p-value 0.01), and anemia (81 of 642 [13%] vs. 46 of 608 [7.6%] respectively, adjusted p-value 0.02). Furthermore, a higher percentage of Black/African American COVID patients (375 of 1,203 [31%]) were noted to receive unfractionated heparin compared to White/Caucasian COVID patients (595 of 2,488 [24%]), for a risk ratio of 1.3 (95% C.I.: [1.17, 1.45], adjusted p-value: 1.6e-5). After balancing upon available clinical covariates, this difference in anticoagulant use remained statistically significant (272 of 959 [28%] for Black/African American vs. 213 of 959 [22%] for White/Caucasian, adjusted p-value: 0.01, relative risk: 1.28, 95% C.I.: [1.09, 1.49]). While retrospective studies cannot suggest any causality, these findings motivate the need for follow-up prospective research in order to elucidate potential socioeconomic, racial, or other disparities underlying the use of anticoagulants to treat severe COVID patients. 

  • Authors:
  • Christian Kirkup1+,
  • Colin Pawlowski1+,
  • Arjun Puranik1,
  • Ian Conrad1,
  • John C. O’Horo2,
  • Dina Gomaa3,
  • Valerie M. Banner-Goodspeed4,
  • Jarrod M Mosier5,
  • Igor Borisovich Zabolotskikh6,
  • Steven K. Daugherty7,
  • Michael A. Bernstein8,
  • Howard A. Zaren9,
  • Vikas Bansal2,
  • Brian Pickering2,
  • Andrew D. Badley2,
  • Rahul Kashyap2,
  • AJ Venkatakrishnan1*,
  • Venky Soundararajan1*
  • 1 nference, Cambridge, MA, 02142, USA
  • 2 Mayo Clinic, Rochester, MN 55905, USA
  • 3 University of Cincinnati, Cincinnati, OH, USA
  • 4 Beth Israel Deaconess Medical Center, Boston, MA, USA
  • 5 Banner University Medical Center, Tucson, AZ, USA
  • 6 Kuban State Medical University, Krasnodar, Russia
  • 7 Cox Medical Center Springfield, IL, USA
  • 8 Stamford Health, Stamford, CT, USA
  • 9 St. Joseph's Candler Health System, Savannah, GA, USA
  • Correspondence:
  • Affiliations:
  • Media coverage:
  • Copyright:
  • The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
  • Affiliations:
  • Media coverage:
  • Copyright:
  • The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Scroll to Top