Does Hydroxychloroquine Prevent Cardiovascular Events in Systemic Lupus Erythematosus Patients?

Background: Systemic lupus erythematosus (SLE) is a chronic, systemic inflammatory disease associated with premature cardiovascular (CV) disease. Hydroxychloroquine (HCQ) is used to control SLE symptoms and has been reported to improve to lipid profiles and prevent venous thromboembolism (VTE) from SLE. However, whether HCQ use can prevent other CV events remains to be examined further.

Objectives: To evaluate the association between HCQ use and CV events in patients with SLE.

Methods: We conducted a nested case-control study within a cohort of SLE patients using the nationwide French health care database (SNDS), which records all in-and outpatient claims, as well as hospital discharges, for more than 65 million inhabitants. SLE patients with at least a follow-up of 5 years in the database were identified over the period from 2010 to 2020 and were followed up to 31 December 2020. Study outcomes consisted of the composite of myocardial infarction (MI), stroke, or VTE, as well as individual components. Each case was the first outcome among the three components that occurred after SLE cohort entry and after a period of 5 years with no occurrence of the same outcome. For each outcome, date of first hospital discharge with the relevant diagnostic code was the index date. Controls were selected using incidence density sampling (case: control ratio up to 1:10) and matched on age, sex, time since first SLE code in the database and time since entry in the database, index date, use of anticoagulants or antiplatelet drugs and use of CV drug in the last year, chronic kidney disease, hospitalization in the last year. HCQ exposure was categorized as current (last HCQ dispensing 1-90 days prior to index date), recent (last dispensing 91-365 days prior), or no dispensing in the year before index date. We used conditional logistic regression to evaluate the association between HCQ exposure and CV events, controlling for prior other CV event for the individual outcomes, and in the previous year, for the dispensing of other SLE treatments or NSAIDs, and number of outpatient visits.

Results: The SLE cohort included 56,544 patients followed for a mean of 10.4 years. We identified 2,355 cases of composite CV outcome, 737 MI, 1032 stroke, 783 VTE, and 22,444 matched controls. Adjusted conditional odd ratios (ORs) (95% CI) for current HCQ use relative to no use in the year preceding index date were 0.57 [0.52 - 0.62] for composite CV events, 0.68 [0.58 - 0.80] for MI, 0.66 [0.57 - 0.75] for stroke, and 0.52 [0.44 - 0.61] for VTE. No significant effect was observed for non-current use of HCQ.

Conclusions: Our study suggests that current use of HCQ protects not only against VTE but also against MI and stroke in patients with SLE.