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Risk Factors for Acute Incident VTE in Ambulatory COVID-19 Patients
Quick Takes
- Among ambulatory patients with COVID-19 infection, the risk of VTE was markedly higher than those without COVID-19 infection.
- A history of COVID-19 vaccination significantly reduced the risk of VTE.
- Patients with inherited thrombophilia had a modestly increased risk of VTE in the post-COVID infection period.
Study Questions:
What is the association between ambulatory coronavirus disease 2019 (COVID-19) and short-term risk of venous thromboembolism (VTE) and the potential protective role of vaccination?
Methods:
The authors used a population-based cohort study of nonhospitalized patients with and without COVID-19 from a United Kingdom (UK) Biobank between March 1, 2020–September 3, 2021. They propensity-score matched patients with COVID-19 to COVID-19-naïve patients during the same period, excluding those with a history of VTE, use of antithrombotic medications, or those who tested positive during a hospitalization. The primary outcome was a composite of VTE within 30 days of COVID-19 infection, adjusted for age, sex, ethnicity, socioeconomic status, obesity, COVID-19 vaccination status, and history of inherited thrombophilia.
Results:
Among 18,818 patients with COVID-19 and 93,179 matched patients without COVID-19, those with an infection had an increased risk of VTE within 30 days of infection (incidence rate 50.99 vs. 2.37 per 1,000 person-years for infected and uninfected patients, respectively; hazard ratio [HR], 21.42; 95% confidence interval [CI], 12.63-36.31). The risk of VTE was attenuated among patients with a history of COVID-19 vaccination (HR, 5.95; 95% CI, 1.82-19.5) as compared to those without COVID-19 vaccination (HR, 27.94; 95% CI, 15.11-51.65; p for interaction = 0.02). Independent predictors of VTE among patients with COVID-19 included older age (HR, 1.87 per 10 years; 95% CI, 1.5-2.33), male sex (HR, 1.69; 95% CI, 1.30-2.19), and obesity (HR, 1.83; 95% CI, 1.15-3.66). Inherited thrombophilia was associated with an increased risk of post-COVID-19 VTE (HR, 2.05; 95% CI, 1.15-3.66).
Conclusions:
The authors concluded that ambulatory COVID-19 infection was associated with a substantial risk of VTE. The authors also concluded that COVID-19 vaccination reduced the overall risk of VTE.
Perspective:
This large UK Biobank cohort has two very important findings for clinical practice. First, the markedly elevated risk of VTE among those with ambulatory COVID-19 infection stands in contrast to prior observational studies and meta-analyses. Second, patients who had previously been vaccinated against COVID-19 had a markedly lower risk of VTE than those without COVID-19 vaccination. In fact, prior vaccination status was a larger predictor of VTE risk than age, male sex, and obesity, all of which are well known VTE risk factors. However, the National Heart, Lung, and Blood Institute–funded ACTIV-4B study found very low rates of VTE among ambulatory patients with COVID-19, and no difference with aspirin or anticoagulation therapy as compared to placebo. However, aside from age >40 years, that study population was not enriched for other VTE risk factors and included a markedly smaller number of patients (657) as compared to this cohort study (111,917). While future prospective studies are needed to determine the role of VTE prophylaxis among high-risk patients with ambulatory COVID-19 infection, this study does provide striking evidence that COVID-19 vaccination provides significant protection against VTE risk when an infection occurs.
Clinical Topics: Anticoagulation Management, COVID-19 Hub, Geriatric Cardiology, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism
Keywords: Aged, Anticoagulants, COVID-19, COVID-19 Vaccines, Ethnic Groups, Fibrinolytic Agents, Obesity, Primary Prevention, Risk Factors, Social Class, Thrombophilia, Vaccination, Vascular Diseases, Venous Thromboembolism
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