Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State
Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State
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DOI：
10.1001/jama.2020.8630
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发表时间：
2020-06-23
影响因子：
120.7
通讯作者：
Zucker, Howard A.
中科院分区：
文献类型：
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作者：
Rosenberg, Eli S.;Dufort, Elizabeth M.;Zucker, Howard A.
要点问题在 2019 年冠状病毒病 (COVID-19) 患者中，使用羟氯喹（联合或不联合阿奇霉素）与院内死亡率之间是否存在关联？结果在一项对纽约大都会住院的 1438 名患者进行的回顾性队列研究中，与两种药物均不治疗的患者相比，单独使用羟氯喹治疗的院内死亡率调整后的风险比为 1.08，单独使用阿奇霉素的为 0.56，羟氯喹和阿奇霉素联合治疗的院内死亡率的调整后的风险比为 1.35。这些风险比均不具有统计显着性。意义在住院的 COVID-19 患者中，使用羟氯喹、阿奇霉素或两者联合治疗与显着降低院内死亡率无关。重要性羟氯喹（无论是否联合阿奇霉素）已被认为是 2019 年冠状病毒病 (COVID-19) 患者的可能治疗药物。然而，关于疗效和相关不良事件的数据有限。目的描述使用羟氯喹（联合或不联合阿奇霉素）与诊断为 COVID-19 的医院住院患者的临床结果之间的关联。设计、设置和参与者回顾性多中心队列研究，对 25 家医院所有入院的经实验室确诊的 COVID-19 患者进行随机抽样，占纽约大都市区 COVID-19 患者的 88.2%。符合条件的患者在 2020 年 3 月 15 日至 28 日期间入院至少 24 小时。从医疗记录中提取药物、既往病史、入院时的临床措施、结果和不良事件。最终随访日期为 2020 年 4 月 24 日。 暴露 接受羟氯喹和阿奇霉素、单独服用羟氯喹、单独服用阿奇霉素，或两者均未服用。主要结果和措施主要结果是院内死亡率。次要结局是心脏骤停和心电图异常（心律失常或 QT 间期延长）。结果在 1438 名诊断为 COVID-19 的住院患者中（858 名 [59.7%] 男性，中位年龄 63 岁），接受羟氯喹、阿奇霉素或两者药物治疗的患者比未接受任一药物的患者更有可能患有糖尿病、呼吸频率 >22/min、胸部影像学异常、O-2 饱和度低于 90%、天冬氨酸转氨酶大于 40 U/L。总体院内死亡率为 20.3%（95% CI，18.2%-22.4%）。接受羟氯喹+阿奇霉素治疗的患者的死亡概率为 189/735 (25.7% [95% CI, 22.3%-28.9%])，单用羟氯喹为 54/271 (19.9% [95% CI, 15.2%-24.7%])，单用阿奇霉素为 21/211 (10.0%) [95% CI, 5.9%-14.0%]），两种药物均无效，28/221 (12.7% [95% CI, 8.3%-17.1%]）。在调整后的 Cox 比例风险模型中，与未接受任何药物治疗的患者相比，接受羟氯喹+阿奇霉素治疗（HR，1.35 [95% CI，0.76-2.40]）、单用羟氯喹治疗（HR，1.08 [95% CI，0.63-1.85]）或单用阿奇霉素治疗（HR，0.56 [95% CI，0.76-2.40]）的患者死亡率没有显着差异。 0.26-1.21]）。在逻辑模型中，与未接受任何药物的患者相比，接受羟氯喹+阿奇霉素（调整后的 OR，2.13 [95% CI，1.12-4.05]）的患者发生心脏骤停的可能性明显更高，但单独使用羟氯喹（调整后的 OR，1.91 [95% CI，0.96-3.81]）或单独使用阿奇霉素（调整后的 OR，0.64 [95% CI，1.12-4.05]）的患者发生心脏骤停的可能性明显更高。 0.27-1.56]），。在调整后的逻辑回归模型中，心电图异常结果的相对可能性没有显着差异。结论和相关性在纽约大都会住院的 COVID-19 患者中，使用羟氯喹、阿奇霉素或两者联合治疗与两种治疗均不治疗相比，与院内死亡率差异没有显着相关性。然而，对这些发现的解释可能受到观察性设计的限制。本研究探讨了 2020 年 3 月在纽约大都市区住院的 COVID-19 患者中使用羟氯喹、阿奇霉素或两者与院内死亡率、心电图变化和心脏骤停之间的关联。
Key PointsQuestionAmong patients with coronavirus disease 2019 (COVID-19), is there an association between use of hydroxychloroquine, with or without azithromycin, and in-hospital mortality? FindingsIn a retrospective cohort study of 1438 patients hospitalized in metropolitan New York, compared with treatment with neither drug, the adjusted hazard ratio for in-hospital mortality for treatment with hydroxychloroquine alone was 1.08, for azithromycin alone was 0.56, and for combined hydroxychloroquine and azithromycin was 1.35. None of these hazard ratios were statistically significant. MeaningAmong patients hospitalized with COVID-19, treatment with hydroxychloroquine, azithromycin, or both was not associated with significantly lower in-hospital mortality.ImportanceHydroxychloroquine, with or without azithromycin, has been considered as a possible therapeutic agent for patients with coronavirus disease 2019 (COVID-19). However, there are limited data on efficacy and associated adverse events. ObjectiveTo describe the association between use of hydroxychloroquine, with or without azithromycin, and clinical outcomes among hospital inpatients diagnosed with COVID-19. Design, Setting, and ParticipantsRetrospective multicenter cohort study of patients from a random sample of all admitted patients with laboratory-confirmed COVID-19 in 25 hospitals, representing 88.2% of patients with COVID-19 in the New York metropolitan region. Eligible patients were admitted for at least 24 hours between March 15 and 28, 2020. Medications, preexisting conditions, clinical measures on admission, outcomes, and adverse events were abstracted from medical records. The date of final follow-up was April 24, 2020. ExposuresReceipt of both hydroxychloroquine and azithromycin, hydroxychloroquine alone, azithromycin alone, or neither. Main Outcomes and MeasuresPrimary outcome was in-hospital mortality. Secondary outcomes were cardiac arrest and abnormal electrocardiogram findings (arrhythmia or QT prolongation). ResultsAmong 1438 hospitalized patients with a diagnosis of COVID-19 (858 [59.7%] male, median age, 63 years), those receiving hydroxychloroquine, azithromycin, or both were more likely than those not receiving either drug to have diabetes, respiratory rate >22/min, abnormal chest imaging findings, O-2 saturation lower than 90%, and aspartate aminotransferase greater than 40 U/L. Overall in-hospital mortality was 20.3% (95% CI, 18.2%-22.4%). The probability of death for patients receiving hydroxychloroquine+azithromycin was 189/735 (25.7% [95% CI, 22.3%-28.9%]), hydroxychloroquine alone, 54/271 (19.9% [95% CI, 15.2%-24.7%]), azithromycin alone, 21/211 (10.0% [95% CI, 5.9%-14.0%]), and neither drug, 28/221 (12.7% [95% CI, 8.3%-17.1%]). In adjusted Cox proportional hazards models, compared with patients receiving neither drug, there were no significant differences in mortality for patients receiving hydroxychloroquine+azithromycin (HR, 1.35 [95% CI, 0.76-2.40]), hydroxychloroquine alone (HR, 1.08 [95% CI, 0.63-1.85]), or azithromycin alone (HR, 0.56 [95% CI, 0.26-1.21]). In logistic models, compared with patients receiving neither drug cardiac arrest was significantly more likely in patients receiving hydroxychloroquine+azithromycin (adjusted OR, 2.13 [95% CI, 1.12-4.05]), but not hydroxychloroquine alone (adjusted OR, 1.91 [95% CI, 0.96-3.81]) or azithromycin alone (adjusted OR, 0.64 [95% CI, 0.27-1.56]), . In adjusted logistic regression models, there were no significant differences in the relative likelihood of abnormal electrocardiogram findings. Conclusions and RelevanceAmong patients hospitalized in metropolitan New York with COVID-19, treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality. However, the interpretation of these findings may be limited by the observational design.This study examines associations between use of hydroxychloroquine, azithromycin, or both and in-hospital mortality, ECG changes, and cardiac arrest among patients with COVID-19 hospitalized in the metropolitan New York area in March 2020.