Risk of Arterial and Venous Thrombotic Events Among Patients with COVID-19: A Multi-National Collaboration of Regulatory Agencies from Canada, Europe, and United States

Clin Epidemiol. 2024 Feb 10:16:71-89. doi: 10.2147/CLEP.S448980. eCollection 2024.

Abstract

Purpose: Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability.

Patients and methods: We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country-level estimates of 90-day absolute risk (with 95% confidence intervals) of ATE and VTE.

Results: The seven cohorts included 1,061,565 patients initially diagnosed with COVID-19 in the ambulatory setting before COVID-19 vaccines were available (through November 2020). The 90-day absolute risk of ATE during this period ranged from 0.11% (0.09-0.13%) in Canada to 1.01% (0.97-1.05%) in the US, and the 90-day absolute risk of VTE ranged from 0.23% (0.21-0.26%) in Canada to 0.84% (0.80-0.89%) in England. The seven cohorts included 3,544,062 patients with COVID-19 during vaccine availability (beginning December 2020). The 90-day absolute risk of ATE during this period ranged from 0.06% (0.06-0.07%) in England to 1.04% (1.01-1.06%) in the US, and the 90-day absolute risk of VTE ranged from 0.25% (0.24-0.26%) in England to 1.02% (0.99-1.04%) in the US.

Conclusion: There was heterogeneity by country in 90-day absolute risk of ATE and VTE after ambulatory COVID-19 diagnosis both before and during COVID-19 vaccine availability.

Keywords: COVID-19; ischemic stroke; myocardial infarction; thromboembolism; venous thromboembolism.

Grants and funding

The Canadian Network for Observational Drug Effect Studies (CNODES) is a core network partner of CoLab and funded by CADTH (grant number C222 360). At the time of this study, CNODES was a collaborating center of the Drug Safety and Effectiveness Network (DSEN) and funded by the Canadian Institutes of Health Research (CIHR, grant numbers DSE-11856 and DSE-146021). Health Canada had no role in data collection, management, or analysis. This project was also supported by Task Order 75F40119F19001 under Master Agreement 75F40119D10037 from the US Food and Drug Administration (FDA). The FDA approved the study protocol, including statistical analysis plan, and reviewed and approved this manuscript. Coauthors from the FDA participated in the result interpretation and in the preparation and decision to submit the manuscript for publication. The FDA had no role in data collection, management, or analysis. The European portion of this project was supported by the European Medicines Agency (EMA) as a specific contract with Erasmus Medical Center, Rotterdam, the Netherlands, under the framework contract number EMA/2018/21/PE, Lot 3. The EMA approved the EU study protocol and reviewed and approved this manuscript. The EMA had no role in data collection, management, or analysis. Additional support was provided by the UK NIHR Oxford Biomedical Research Centre.