Increased risk of venous thromboembolism in patients with Rheumatoid Arthritis

Image: CC/James Heilman

Key study points:

1. Rheumatoid arthritis is associated with a two-fold increased risk of venous thromboembolism compared to the general population and this heightened risk remains stable over a median followup time of 5.8 years.
2. Hospitalization is a risk factor for venous thromboembolism within the first year after discharge.

Primer: Cardiovascular (CV) disease is the most common cause of mortality in patients with rheumatoid arthritis (RA) and is disproportionately overrepresented in this group. However, studies have suggested that the increased incidence of CV events in patients with RA is independent of the traditional CV risk factors including age, sex, smoking history, diabetes, hypertension, dyslipidemia, and BMI. These findings indicate that, perhaps RA may affect the systemic vasculature in a manner different from the traditional atherosclerotic vessel change seen in the general population. Indeed, autoimmune conditions such as RA have been associated with diseases of hypercoagulability and recent studies suggest that RA may confer an increased risk of venous thromboembolism (VTE) (Relative Risk = 1.99). However, these findings are limited as the studies were either conducted in the hospital population, where many factors shared between the RA and non-RA groups may confound the results, or were not sufficiently large to provide strong conclusions. To lend strength to these previous studies, the authors of this article sought to investigate rates and risk factors for VTE in a large, population-based sample of RA patients.

Background reading:

1. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors [Arthritis and Rheumatism]

2. Risk of venous thromboembolism with rheumatoid arthritis [Thrombosis and Haemostasis]

3. Noncardiac vascular disease in rheumatoid arthritis: Increase in venous thromboembolic events? [Arthritis and Rheumatism]

This [prospective, population-based cohort] study: The study focused on two cohorts: (1) The prevalence cohort studied RA patients that were receiving followup and allowed for assessment of average VTE risk; (2) The incidence cohort followed patients newly diagnosed with RA within 12 months of symptom onset to assess risk as a function of time since onset of RA. 37,856 patients with RA in the prevalence cohort were compared to 169,921 age-, sex-, and location-matched controls. 7,904 patients with RA in the incident cohort were compared to 37,350 matched controls. Statistical analysis revealed several key findings.

1. Overall, the rate of VTE in RA patients was 5.9 (CI: 5.1-6.6) per 1,000 person-years. Compared the VTE rate in matched controls (2.8 (CI: 2.6-3.1) per 1,000 person-years) controls, having RA conferring a hazard ratio of 2.0 (CI: 1.9-2.2, p<0.001).

2. Within a median of 5.8 years after initial diagnosis, the rate of VTE occurrence is 4.5 (CI: 3.0-5.9) per 1,000 person years in those with RA. During the same time period, the rate of VTE in matched controls was 1.6 (CI: 1.4-1.9).

3. Patients with and without RA experienced a 5-fold increased risk of VTE during the first year after hospitalization.

In sum: These findings of this study indicate that within the first year of their initial diagnosis, patients with RA have a 2-fold increased risk of developing VTE compared to their non-RA counterparts and this heightened risk does not decrease with duration of illness. Further, hospitalization increases risk of VTE 5-fold within the first year after discharge, regardless of RA status.

This study faces several limitations. First, the primary and secondary outcomes (VTE and DVT/PE, respectively) assessed are dependent on correct diagnosis, thus the results may be affected by misclassification errors. Second, the authors did not account for potential VTE risk factors (e.g. immobilization) that may be associated with RA and, therefore, could potentially confound the results. Third, it has been established that this autoimmune disease confers increased CV risk. Thus, patients with RA may have been followed with increased diligence by their care providers, therefore resulting in a surveillance bias. Nevertheless, this is the largest population-based study of VTE risk in RA patients to date.

Click to read the study in JAMA (Journal of the American Medical Association)

Written by [MK]

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