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.

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撤回：羟氯喹或氯喹联合或不联合大环内酯类药物治疗 COVID-19：一项跨国登记分析


羟氯喹或氯喹通常与第二代大环内酯类药物联合使用，被广泛用于治疗 COVID-19，尽管没有确凿的证据表明它们的益处。尽管在用于自身免疫性疾病或疟疾等已批准的适应症时通常是安全的，但这些治疗方案在 COVID-19 中的安全性和益处评价较差。我们对羟氯喹或氯喹联合或不联合大环内酯类药物治疗 COVID-19 的使用进行了跨国登记分析。该登记系统包含来自六大洲 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呈 SARS-CoV-2 阳性的患者。在诊断后 48 小时内接受一种感兴趣的治疗的患者被纳入四个治疗组之一（单独使用氯喹、氯喹与大环内酯类药物、单独使用羟氯喹或羟氯喹与大环内酯类药物），并且未接受这些治疗的患者形成对照组。诊断后 48 小时以上或接受机械通气时开始其中一种治疗的患者以及接受瑞德西韦治疗的患者被排除在外。感兴趣的主要结局是院内死亡率和新发室性心律失常（非持续或持续性室性心动过速或心室颤动）的发生。 96 032 名 COVID-19 患者（平均年龄 53·8 岁，46·3% 女性）在研究期间住院并符合纳入标准。 其中，14 888 名患者属于治疗组（1868 名患者接受氯喹治疗，3783 名患者接受氯喹联合大环内酯治疗，3016 名患者接受羟氯喹联合治疗，6221 名患者接受羟氯喹联合大环内酯治疗），81 144 名患者属于对照组。 10 698（11·1%）例患者在医院死亡。在控制多种混杂因素（年龄、性别、种族或民族、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、免疫抑制状况和基线疾病严重程度）后，与死亡率相比对照组 (9·3%)、羟氯喹 (18·0%; 风险比 1·335, 95% CI 1·223–1·457)、羟氯喹联合大环内酯组 (23·8%; 1·447, 1 ·368–1·531)、氯喹 (16·4%; 1·365、1·218–1·531) 和氯喹与大环内酯 (22·2%; 1·368、1·273–1·469) ）均与院内死亡风险增加独立相关。与对照组（0·3%）、羟氯喹（6·1%；2·369、1·935–2·900）、羟氯喹联合大环内酯组（8·1%；5·106、4·106– 5·983）、氯喹（4·3%；3·561、2·760–4·596）和氯喹与大环内酯（6·5%；4·011、3·344–4·812）独立地与住院期间新发室性心律失常的风险增加相关。我们无法确认羟氯喹或氯喹单独使用或与大环内酯类药物一起使用时对 COVID-19 住院结果的益处。当用于治疗 COVID-19 时，这些药物方案中的每一种都与院内生存率降低和室性心律失常频率增加相关。威廉·哈维 (William Harvey) 布莱根妇女医院高级心血管医学杰出主席。