Objective. The antimalarial medication hydroxychloroquine has been proposed as a thromboprotective agent in systemic lupus erythematosus (SLE), but studies thus far have been limited by the possibility of confounding by indication. This study was conducted to assess whether exposure to antimalarial drugs is associated with a decrease in thrombovascular events (TEs) in patients with SLE.Methods. The study was designed as a nested case-control study embedded in an inception cohort of patients with SLE, which allowed adjustments for possible confounding by calendar year, duration of disease, duration of observation, and severity of lupus. After controlling for the possible confounding variables in conditional logistic regression models, the use of antimalarial drugs was assessed for its effects on the development of TEs in lupus patients.Results. Fifty-four cases of TE were identified, and these were matched with 108 control subjects (lupus patients without TEs). Univariate analyses identified older age (odds ratio [OR] 1.04, 95% confidence interval [95%CI] 1.01-1.07) or being older than age 50 years (OR 3.5, 95% CI 1.4-8.6) and ever having hypertension (OR 2.5, 95% CI 1.0-5.8) as being associated with an increased risk of TEs, whereas use of antimalarial drugs (OR 0.31, 95% CI 0.13-0.71) was associated with a decreased risk of TEs. Separate analyses were done for arterial and venous TEs, which yielded similar results. In multivariate analyses, use of antimalarial drugs (OR 0.32, 95% CI 0.14-0.74) and older age (OR 1.04, 95% CI 1.01-1.07) were the only 2 variables that remained significant.Conclusion. The results from this nested casecontrol study demonstrate that, after accounting for the effects of disease severity, disease duration, and calendar year, antimalarial drugs were found to be thromboprotective, being associated with a 68% reduction in the risk of all TEs, with a range of risk reduction of at least 26% up to as high as 86%.Systemic lupus erythematosus (SLE) is a systemic illness of autoimmune etiology, characterized by either acute or chronic inflammation of multiple organs. The prevalence of SLE in North America is ϳ40 per 100,000 people (1,2), and more than 80% of cases occur in women who develop the illness during their childbearing years. As a consequence, the disease may affect as many as 1 in 1,000 young women. The risk of arterial, venous, or small-vessel thrombovascular events (TEs) in a patient with SLE is significantly higher than that in the
