Liao Yu, Liu Ping-Yen, Huang Mu-Shiang, Mau Yu-Lin, Su Pei-Fang, Huang Ting-Chun
Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University.
Institute of Clinical Medicine, College of Medicine.
Acta Cardiol Sin. 2022 Nov;38(6):723-735. doi: 10.6515/ACS.202211_38(6).20220415A.
Hydroxychloroquine is used as an antimalarial and immunomodulator, however it can induce QT prolongation that could potentially lead to fatal arrhythmia. We investigated changes in QT interval in long-term hydroxychloroquine users, and identified possible risk factors associated with significant QTc prolongation.
We retrospectively enrolled 3603 patients who received long-term hydroxychloroquine treatment from 2009 to 2019, of whom 167 had electrocardiography (ECG) results before and during hydroxychloroquine therapy. Baseline characteristics, laboratory data, comorbidities, concurrent medications, and related clinical outcomes were reviewed.
Overall, 225 patients (6.2%) died within the study period, with 50 patients (1.4%) continuously receiving hydroxychloroquine treatment until death. Three patients had fatal ventricular arrhythmia. No significant change in corrected QT interval (QTc) was noted before and during hydroxychloroquine treatment (451.1 ± 39.9 ms vs. 456.0 ± 37.3 ms, P = 0.140) in the ECG cohort. Multivariable logistic regression showed that diabetes mellitus [odds ratio (OR): 9.55, 95% confidence interval (CI): 2.02-45.22; = 0.005] and use of additional QT-prolonging drugs (OR: 2.89, 95% CI: 1.40-5.94; = 0.004) were independent risk factors for significant QTc prolongation. Multiple linear regression, with the number of QT-prolonging drugs and comorbidities including diabetes mellitus, hypertension, and atrial fibrillation as explanatory variables, predicted QTc response (adjusted R = 0.385) in the long-term hydroxychloroquine users.
In the long-term users of hydroxychloroquine, those with diabetes mellitus and concurrent use of additional QT-prolonging drugs were at a higher risk of significant QTc prolongation. Baseline QTc interval, concurrent medications, and comorbidities predicted QTc response.
羟氯喹被用作抗疟药和免疫调节剂，然而它可导致QT间期延长，这可能会引发致命性心律失常。我们研究了长期使用羟氯喹患者的QT间期变化，并确定了与显著QTc延长相关的可能危险因素。
我们回顾性纳入了2009年至2019年期间接受长期羟氯喹治疗的3603例患者，其中167例在羟氯喹治疗前和治疗期间有心电图（ECG）结果。对基线特征、实验室数据、合并症、同时使用的药物以及相关临床结局进行了评估。
总体而言，225例患者（6.2%）在研究期间死亡，50例患者（1.4%）直至死亡一直接受羟氯喹治疗。3例患者发生致命性室性心律失常。在心电图队列中，羟氯喹治疗前和治疗期间校正QT间期（QTc）无显著变化（451.1±39.9毫秒对456.0±37.3毫秒，P=0.140）。多变量逻辑回归显示，糖尿病[比值比（OR）：9.55，95%置信区间（CI）：2.02-45.22；P=0.005]和使用其他延长QT间期的药物（OR：2.89，95%CI：1.40-5.94；P=0.004）是显著QTc延长的独立危险因素。以延长QT间期的药物数量以及包括糖尿病、高血压和心房颤动在内的合并症作为解释变量的多元线性回归，预测了长期使用羟氯喹患者的QTc反应（调整R=0.385）。
在长期使用羟氯喹的患者中，患有糖尿病且同时使用其他延长QT间期药物的患者发生显著QTc延长的风险更高。基线QTc间期、同时使用的药物和合并症可预测QTc反应。
