Mehra Mandeep R, Desai Sapan S, Ruschitzka Frank, Patel Amit N
Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA.
Surgisphere Corporation, Chicago, IL, USA.
Lancet. 2020 May 22. doi: 10.1016/S0140-6736(20)31180-6.
Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19.
We did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation).
96 032 patients (mean age 53·8 years, 46·3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11·1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223-1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368-1·531), chloroquine (16·4%; 1·365, 1·218-1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273-1·469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935-2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106-5·983), chloroquine (4·3%; 3·561, 2·760-4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344-4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation.
We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.
William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women's Hospital.
羟氯喹啉或氯喹啉，通常与第二代大环内酯类药物联合使用，尽管尚无确凿证据证明其疗效，但仍被广泛用于治疗2019冠状病毒病（COVID-19）。虽然这些药物用于自身免疫性疾病或疟疾等获批适应症时通常是安全的，但在COVID-19中这些治疗方案的安全性和疗效评估不足。
我们对使用羟氯喹啉或氯喹啉联合或不联合大环内酯类药物治疗COVID-19进行了一项多国登记分析。该登记包含来自六大洲671家医院的数据。我们纳入了2019年12月20日至2020年4月14日期间住院且实验室检测结果为严重急性呼吸综合征冠状病毒2（SARS-CoV-2）阳性的患者。在诊断后48小时内接受其中一种感兴趣治疗的患者被纳入四个治疗组之一（单独使用氯喹啉、氯喹啉联合大环内酯类药物、单独使用羟氯喹啉或羟氯喹啉联合大环内酯类药物），未接受这些治疗的患者形成对照组。诊断后超过48小时或在机械通气时开始使用其中一种感兴趣治疗的患者，以及接受瑞德西韦治疗的患者被排除。主要关注的结局是住院死亡率和新发室性心律失常（非持续性或持续性室性心动过速或心室颤动）的发生情况。
在研究期间，96032例COVID-19患者（平均年龄53.8岁，46.3%为女性）住院并符合纳入标准。其中，14888例患者在治疗组（1868例接受氯喹啉治疗，3783例接受氯喹啉联合大环内酯类药物治疗，3016例接受羟氯喹啉治疗，6221例接受羟氯喹啉联合大环内酯类药物治疗），81144例患者在对照组。10698例（11.1%）患者在医院死亡。在控制了多个混杂因素（年龄、性别、种族或族裔、体重指数、潜在心血管疾病及其危险因素、糖尿病、潜在肺部疾病、吸烟、免疫抑制状态和基线疾病严重程度）后，与对照组死亡率（9.3%）相比，羟氯喹啉（18.0%；风险比1.335，95%置信区间1.223 - 1.457）、羟氯喹啉联合大环内酯类药物（23.8%；1.447，1.368 - 1.531）、氯喹啉（16.4%；1.365，1.218 - 1.531）和氯喹啉联合大环内酯类药物（22.2%；1.368，1.273 - 1.469）均与住院死亡率增加独立相关。与对照组（0.3%）相比，羟氯喹啉（6.1%；2.369，1.935 - 2.900）、羟氯喹啉联合大环内酯类药物（8.1%；5.106，4.106 - 5.983）、氯喹啉（4.3%；3.561，2.760 - 4.596）和氯喹啉联合大环内酯类药物（6.5%；4.011，3.344 - 4.812）均与住院期间新发室性心律失常风险增加独立相关。
我们无法证实单独使用或与大环内酯类药物联合使用羟氯喹啉或氯喹啉对COVID-19患者的住院结局有益。这些药物方案中的每一种在用于治疗COVID-19时均与住院生存率降低和室性心律失常频率增加相关。
布莱根妇女医院高级心血管医学威廉·哈维杰出主席基金。
