Department of Epidemiology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Department of Medical Informatics, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Eur J Prev Cardiol. 2022 Feb 3;28(17):1875-1882. doi: 10.1093/eurjpc/zwaa118.
: Hydroxychloroquine and chloroquine ([hydroxy]chloroquine) are drugs used to treat malaria and rheumatological disorders and were recently suggested as beneficial for prevention and treatment of patients with coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection. However, longitudinal studies to assess the electrocardiographic and cardiotoxic effects of these drugs are limited. In this study, we aimed to investigate the effect of these drugs on QTc-interval and incidence of sudden cardiac death (SCD).
We designed a longitudinal follow-up study of individuals within the prospective population-based Rotterdam Study. Eligible individuals had available data on medication and repeated ECG measurements. The study period was between 1 January 1991 and 1 January 2014. We studied on current and past use of [hydroxy]chloroquine as a time-varying exposure; high versus low daily dose of [hydroxy]chloroquine. QTc-interval duration, and the occurrence of SCD were the main outcomes. SCD was defined as an unexpected and sudden death due to cardiac arrhythmia within one hour of the onset of acute symptoms, and in patients without cardiac symptoms within 24 hours before death.
Among the study population of 14 594 individuals (58.8% women) with an average age of 65 years, 346 patients used [hydroxy]chloroquine at any time during follow-up. The total number of SCD cases was 609. In a multiple linear mixed model analysis, the current use of [hydroxy]chloroquine was associated with a significantly increased duration of the QTc-interval of 8.1 ms (95% CI: 3.6; 12.6) compared with non-users. The association was stronger among current-high daily dosage [15.3 (95%CI: 7.0; 23.6)] compared with current-low daily dosage [5.5 (95%CI: 0.4; 10.7)] users. In a Cox proportional hazard regression analysis, the risk of SCD was significantly higher in participants who were current users of [hydroxy]chloroquine than in non-users [adjusted hazard ratio; 3.7 (95%CI: 1.1; 12.6)].
In this longitudinal study, persons who received [hydroxy]chloroquine had an increased QTc-interval duration and the association was dose-dependent. [Hydroxy]chloroquine was associated with a significantly increased risk of SCD. As long as their activity against COVID-19 is controversial, cardiotoxicity is a strong argument against using these drugs to treat COVID-19 infections.
羟氯喹和氯喹（[羟基]氯喹）是用于治疗疟疾和风湿性疾病的药物，最近由于 SARS-CoV-2 感染，有人提出它们对预防和治疗 2019 年冠状病毒病（COVID-19）患者有益。然而，评估这些药物的心电图和心脏毒性的纵向研究是有限的。在这项研究中，我们旨在研究这些药物对 QTc 间期和心脏性猝死（SCD）发生率的影响。
我们设计了一项对前瞻性人群基础的鹿特丹研究中个体的纵向随访研究。符合条件的个体有药物和重复心电图测量的数据。研究期间为 1991 年 1 月 1 日至 2014 年 1 月 1 日。我们研究了[羟基]氯喹的当前和过去使用情况，作为时间变化的暴露；[羟基]氯喹的高与低日剂量。主要结局为 QTc 间期持续时间和 SCD 的发生。心脏性猝死定义为急性症状发作后 1 小时内因心律失常而突然意外死亡，且在死亡前 24 小时内无心脏症状的患者。
在 14594 名（58.8%为女性）平均年龄为 65 岁的研究人群中，有 346 名患者在随访期间任何时候使用[羟基]氯喹。总心脏性猝死病例为 609 例。在多线性混合模型分析中，与未使用者相比，当前使用[羟基]氯喹的 QTc 间期延长 8.1ms（95%CI：3.6；12.6）。与当前低日剂量[5.5（95%CI：0.4；10.7）]使用者相比，当前高日剂量[15.3（95%CI：7.0；23.6）]使用者的关联更强。在 Cox 比例风险回归分析中，与未使用者相比，当前使用[羟基]氯喹的参与者发生 SCD 的风险明显更高[校正后的危险比；3.7（95%CI：1.1；12.6）]。
在这项纵向研究中，接受[羟基]氯喹治疗的患者 QTc 间期延长，且这种关联呈剂量依赖性。[羟基]氯喹与心脏性猝死的风险显著增加相关。只要它们对 COVID-19 的活性存在争议，心脏毒性就是反对用这些药物治疗 COVID-19 感染的一个强有力的论据。
