Cardiology Department, Pasteur University Hospital, Nice, France.
Cardiology Department, Clinique la Casamance, Aubagne, France.
Clin Pharmacol Ther. 2020 Nov;108(5):1090-1097. doi: 10.1002/cpt.1968. Epub 2020 Jul 20.
Association between Hydroxychloroquine (HCQ) and Azithromycin (AZT) is under evaluation for patients with lower respiratory tract infection (LRTI) caused by the Severe Acute Respiratory Syndrome (SARS-CoV-2). Both drugs have a known torsadogenic potential, but sparse data are available concerning QT prolongation induced by this association. Our objective was to assess for COVID-19 LRTI variations of QT interval under HCQ/AZT in patients hospitalized, and to compare manual versus automated QT measurements. Before therapy initiation, a baseline 12 lead-ECG was electronically sent to our cardiology department for automated and manual QT analysis (Bazett and Fridericia's correction), repeated 2 days after initiation. According to our institutional protocol (Pasteur University Hospital), HCQ/AZT was initiated only if baseline QTc ≤ 480ms and potassium level> 4.0 mmol/L. From March 24 to April 20 2020, 73 patients were included (mean age 62 ± 14 years, male 67%). Two patients out of 73 (2.7%) were not eligible for drug initiation (QTc ≥ 500 ms). Baseline average automated QTc was 415 ± 29 ms and lengthened to 438 ± 40 ms after 48 hours of combined therapy. The treatment had to be stopped because of significant QTc prolongation in two out of 71 patients (2.8%). No drug-induced life-threatening arrhythmia, nor death was observed. Automated QTc measurements revealed accurate in comparison with manual QTc measurements. In this specific population of inpatients with COVID-19 LRTI, HCQ/AZT could not be initiated or had to be interrupted in less than 6% of the cases.
羟氯喹(HCQ)和阿奇霉素(AZT)联合用于治疗由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2)引起的下呼吸道感染(LRTI)。这两种药物都有已知的致扭转型潜力,但关于这种联合用药引起的 QT 延长的数据很少。我们的目的是评估 COVID-19 LRTI 患者在接受 HCQ/AZT 治疗前后 QT 间期的变化,并比较手动和自动 QT 测量。在开始治疗前,将基线 12 导联心电图通过电子方式发送到我们的心脏病科,进行自动和手动 QT 分析(Bazett 和 Fridericia 校正),在开始治疗后 2 天重复。根据我们的机构方案(巴斯德大学医院),只有在基线 QTc≤480ms 且钾水平>4.0mmol/L 的情况下,才开始使用 HCQ/AZT。从 2020 年 3 月 24 日至 4 月 20 日,共纳入 73 例患者(平均年龄 62±14 岁,男性 67%)。由于有 2 例患者(2.7%)不符合药物起始标准(QTc≥500ms),因此未开始使用该药物。基线时自动测量的平均 QTc 为 415±29ms,联合治疗 48 小时后延长至 438±40ms。有 2 例患者(2.8%)因 QTc 显著延长而停止治疗。未观察到药物引起的危及生命的心律失常或死亡。与手动 QTc 测量相比,自动 QTc 测量更准确。在这组特定的 COVID-19 LRTI 住院患者中,不到 6%的患者无法开始或不得不中断 HCQ/AZT 的治疗。