The risk of venous thromboembolic events in adult patients with systemic lupus erythematosus: a systematic review and meta-analysis

Pooley N, Yazdany J, Langham J, Nicholson L, Langham S, Embleton N, Wang X, Desta B, Barut V, Hammond ER. The risk of venous thromboembolic events in adult patients with systemic lupus erythematosus: a systematic review and meta-analysis. Ann Rheum Dis 2019;78(Suppl 2):A804

Abstract

Background: Although observational studies suggest people with systemic lupus erythematosus (SLE) have a heightened risk of venous thromboembolic events (VTE), meta-analyses that integrate evidence across studies to estimate the pooled risk have not been performed.

Objectives: To conduct a systematic review and meta-analysis to estimate the risk of VTE including pulmonary embolism (PE) and deep vein thrombosis (DVT) in patients with SLE.

Methods: We conducted a systematic review using MEDLINE and EMBASE from inception to March 2018 to identify observational studies (cohort and cross-sectional) that evaluated the risk of several major cardiovascular outcomes in patients with SLE compared to a general population or healthy controls (protocol published in PROSPERO 2018 CRD42018098690). Here we report the results for venous thromboembolic outcomes. Studies were included that provided effect estimates (relative risks or hazard ratios) for the calculation of pooled effect estimates. Random effects models were used to calculate pooled risk ratios (RR) and 95% confidence intervals (CI) separately for VTE, PE and DVT. Visualization of funnel plots and the Egger’s test were used for evaluation of publication bias. The robustness of the results was tested using the leave one out function. Sensitivity analysis assessed the impact of removing high risk of bias studies (i.e. cross-sectional).

Results: A total of 9 studies were identified for inclusion into the meta-analysis; 7 for VTE (including two cross-sectional studies), 3 for DVT and 4 for PE. Meta-analysis of the VTE studies showed a significantly increased RR of 3.67 (95% CI: 2.10 to 6.42) for patients with SLE compared to a general population. Removing the two cross-sectional studies did not impact the results (RR 4.06 [95% CI: 3.12 to 5.28]). The pooled RRs for PE and DVT were 4.47 (95% CI: 1.79 to 11.15) and 5.51 (95% CI: 2.27 to 13.39), respectively. The statistical heterogeneity was high with an I2 ranging between 92% and 99%. Visual examination of the funnel plots showed evidence of publication bias, however this was not supported by the Egger’s test. The leave one out function confirmed the robustness of the results.

Conclusion: Overall, the risk of VTE was found to be significantly higher, over three- to six-fold higher, among patients with SLE compared with the general population. Future research should focus on assessing the impact of traditional and SLE-specific modifiable risk factors on VTE to further identify SLE patients most at risk to support targeting prevention and treatment strategies.

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Systemic lupus erythematosus; stroke and myocardial infarction risk: a systematic review and meta-analysis

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The increasing use and acceptance of alternative statistical approaches to indirect comparison in the NICE HTA submission process