Effect of Triple Combination Therapy With Lopinavir-Ritonavir, Azithromycin, and Hydroxychloroquine on QT Interval and Arrhythmic Risk in Hospitalized COVID-19 Patients

Abstract

Introduction No data are provided about the effect of triple combination therapy with Lopinavir/Ritonavir (LPN/RTN), hydroxychloroquine (HQ) and azithromycin (AZT) on corrected QT (QTc) interval and arrhythmic risk, in COVID-19 patients. This study aims to describe the incidence of extreme QTc interval prolongation among COVID-19 patients on this experimental treatment and to identify the clinical features associated with extreme QTc prolongation. Materials and Methods Data of 87 COVID-19 patients, treated with triple combination including LPN/RTN, HQ and AZT, were analyzed. QT interval was obtained by the tangent method and corrected for heart rate using Bazett’s formula. Extreme QTc interval prolongation was considered an absolute QTc interval ≥ 500 ms or an increase in QTc intervals of 60 ms or greater (ΔQTc ≥ 60 ms) compared with baseline. Results Hypertension (66.7%) and diabetes (25.3%) were the most prevalent cardiovascular comorbidities. Twenty patients (23%) showed extreme QTc interval prolongation; no clinical, electrocardiographic or pharmacological characteristics have been associated to extreme QTc prolongation, except the history of ischemic stroke ( P= 0,007 ). One torsade de pointes (TdP) in patient with QTc extreme prolongation (QTc: 560 ms) after 5 days of therapy was recorded. Conclusions We observed a high incidence of extreme QTc interval prolongation among COVID-19 patients on triple combination therapy. Since the incidence of malignant arrhythmias seems to be not negligible, a careful electrocardiographic monitoring would be advisable.

Higher Rate of Hyperbilirubinemia and Arrythmia in COVID-19 Cases Receiving Combination Therapy Atazanavir /ritonavir vs. Lopinavir /ritonavir

“…In Bessiere et al study, combination therapy with hydroxychloroquine and azithromycin caused prolonged Q-T in 10.7-36% of patients [23]. Russo et al study showed that 23% of patients reached developed arrhythmias following the treatment of COVID-19 with hydroxychloroquine and azithromycin [24]. The results of Moyle G et al study, revealed a meaningful decrease in unconjugated and total bilirubin following zinc sulfate (ZnSO4) intake and a limited decrease in ATV/r plasma exposure.…”

Darunavir/Cobicistat Is Associated with Negative Outcomes in HIV-Negative Patients with Severe COVID-19 Pneumonia

“…Previous articles have notified a clinically significant DDI among hydroxychloroquine, azithromycin, and ritonavir in patients with COVID-19 pneumonia that led to prolonged QT interval. 10,28 Drug Interactions Checker reports reveal a potential weak interaction between hydroxychloroquine and DRV/c and no interaction with azithromycin, but coadmin-istration has not been studied and it is not known if the interaction is clinically relevant. DRV/c could potentially increase hydroxychloroquine exposure by inhibition of P450 enzymes, but dose adjustment is not recommended.…”

Prognostic Value of Fibrinogen among COVID-19 Patients Admitted to an Emergency Department: An Italian Cohort Study

“…According to these findings, routine testing of clotting factors should be integrated with current triage strategies for patients with suspected COVID-19 [ 20 ] in order to collect more detailed information for their clinical management. The potential association between antithrombotic therapy and the clinical presentation of COVID-19 is still debated [ 21 ], and further studies are necessary to evaluate the possible role of clotting factors, in particular fibrinogen, in guiding the use of antiviral and antithrombotic therapies [ 22 , 23 , 24 ] as part of routine medical therapy during hospitalization.…”