• Luigi Moschini, Marco Loffi, Valentina Regazzoni, Giuseppe Di Tano, Elisa Gherbesi, and Gian Battista Danzi.
• Division of Cardiology, Ospedale di Cremona, Viale Concordia 1, 26100, Cremona, Italy.
• Heart Vessels. 2021 Jan 1; 36 (1): 115-120.

IntroductionMost of the drugs associations that have been used to treat patients with SARS-CoV-2 infection increase the risk of prolongation of the corrected QT interval (QTc).ObjectiveTo evaluate the effects of an association therapy of hydroxychloroquine (HY) plus ritonavir/darunavir (RD) or azithromycin (AZ) on QTc intervals.MethodsAt the beginning of COVID-19 pandemic patients admitted to our hospital were treated with the empiric association of HY/RD; one week later the therapeutic protocol was modified with the combination of HY/AZ. Patients underwent an ECG at baseline, then 3 and 7 days after starting therapy. We prospectively enrolled 113 patients (61 in the HY/RD group-52 in the HY/AZ group).ResultsA significant increase in median QTc was reported after seven days of therapy in both groups: from 438 to 452 ms in HY/RD patients; from 433 to 440 ms in HY/AZ patients (p = 0.001 for both). 23 patients (21.2%) had a QTc > 500 ms at 7 days. The risk of developing a QTc > 500 ms was greater in patients with prolonged baseline QTc values (≥ 440 ms for female and ≥ 460 ms for male patients) (OR 7.10 (95% IC 1.88-26.81); p = 0.004) and in patients with an increase in the QTc > 40 ms 3 days after onset of treatment (OR 30.15 (95% IC 6.96-130.55); p = 0.001). One patient per group suffered a malignant ventricular arrhythmia.ConclusionHydroxychloroquine with both ritonavir/darunavir or azithromycin therapy significantly increased the QTc-interval at 7 days. The risk of developing malignant arrhythmias remained relatively low when these drugs were administered for a limited period of time.

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