Association of Hydroxychloroquine Dose With Adverse Cardiac Events in Patients With Systemic Lupus Erythematosus

Abstract

Objective To determine whether hydroxychloroquine (HCQ) dose is associated with adverse cardiac outcomes in patients with systemic lupus erythematosus (SLE). Methods Patients with SLE taking HCQ and with ≥1 echocardiogram followed at a tertiary care center in the Bronx, New York between 2005 and 2021 were included. The HCQ weight‐based dose at the HCQ start date was the main exposure of interest. The outcome was incident all‐cause heart failure with reduced ejection fraction (HFrEF), life‐threatening arrhythmia, or cardiac death. We used Fine‐Gray regression models with death as a competing event to study the association of HCQ dose with the outcome. Due to a significant interaction between smoking and HCQ exposure, models were stratified by smoking status. Propensity score analysis was performed as a secondary analysis. Results Of 294 patients, 37 (13%) developed the outcome over a median follow‐up time of 7.9 years (interquartile range [IQR] 4.2–12.3 years). In nonsmokers (n = 226), multivariable analysis adjusted for age, body mass index, hypertension, chronic kidney disease, diabetes mellitus, and thromboembolism showed that higher HCQ weight‐based doses were not associated with an increased risk of the outcome (subdistribution hazard ratio [HR] 0.62 [IQR 0.41–0.92], P = 0.02). Similarly, higher baseline HCQ doses were not associated with a higher risk of the outcome among smokers (n = 68) (subdistribution HR 0.85 [IQR 0.53–1.34] per mg/kg, P = 0.48). Propensity score analysis showed comparable results. Conclusion Higher HCQ doses were not associated with an increased risk of HFrEF, life‐threatening arrhythmia, or cardiac death among patients with SLE and may decrease the risk among nonsmokers.