Abstract 10203: Effect of Hydroxychloroquine on Endothelial Function in Older Adults with Moderate-Severe Sleep Apnea: A Randomized Clinical Trial

Abstract

Introduction: Obstructive sleep apnea (OSA) is considered a low-grade chronic inflammatory disease. OSA impairs endothelial function and increases cardiovascular mortality. Hydroxychloroquine (HCQ), an anti-inflammatory drug, seems to reduce cardiovascular mortality. In animal and in vitro models, HCQ improved endothelial function. Its effects on endothelial function of patients with OSA is unknown. Hypothesis: Hydroxychloroquine can improve endothelial function in patients with OSA. Methods: Adults older than 65 years with an apnea-hypopnea index (AHI) greater than 15 events/hour were allocated to receive either 400mg of HCQ or placebo daily for eight-weeks. The randomization was computer-generated and pharmacy-controlled. Participants and outcome evaluators were blinded to the group allocation. Home sleep apnea test and measurements of flow-mediated dilation of brachial artery (FMD) and peripheral artery tonometry (PAT) were performed at baseline and follow-up in a research facility. The primary outcomes were the change in FMD (Δ%FMD) and change in PAT reactive-hyperemia index (ΔRHI). Change in AHI (ΔAHI) was a secondary outcome. Generalized estimating equations were used to verify time*group interaction. Results: Fourteen patients were assigned to the HCQ group and fifteen patients to the placebo group between April 2019 and May 2020 with no losses to follow-up. The recruitment was interrupted due to COVID-19 pandemic. Mean Δ%FMD was 0.35 (95% CI –4.26 to 4.97) in placebo group and 0.48 (95% CI –4.08 to 5.04) in HCQ group. Mean ΔRHI was 0.02 (95% CI -0.11 to 0.07) in placebo group and 0.05 (95% CI -0.24 to 0.13) in HCQ group. Mean ΔAHI was 7 (95% CI -1 to 15) in placebo group and -4 (95% CI -11 to 2) in HCQ group. P values for time*group interaction were 0.97, 0.74 and 0.04, respectively. No important adverse events have occurred. Conclusions: In this trial, HCQ did not improve endothelial function measured by FMD and PAT in older adults with OSA. A slight but significant reduction in AHI was observed in HCQ group, suggesting that some specific inflammatory mechanisms participate in OSA causation that could become a future therapeutic approach.