Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring

• Published in: Journal of the American Heart Association Vol. 9; no. 12; p. e017144
• Main Authors: Ramireddy, Archana, Chugh, Harpriya, Reinier, Kyndaron, Ebinger, Joseph, Park, Eunice, Thompson, Michael, Cingolani, Eugenio, Cheng, Susan, Marban, Eduardo, Albert, Christine M, Chugh, Sumeet S
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 16.06.2020; Wiley
• Subjects: Anti-Bacterial Agents - therapeutic use; Antimalarials - therapeutic use; azithromycin; Azithromycin - therapeutic use; Betacoronavirus; Coronavirus Infections - complications; Coronavirus Infections - drug therapy; COVID-19; Drug Therapy, Combination; Electrocardiography - drug effects; Female; Humans; hydroxychloroquine; Hydroxychloroquine - therapeutic use; Long QT Syndrome - chemically induced; Long QT Syndrome - physiopathology; Male; Middle Aged; monitoring; Original Research; Pandemics; Pneumonia, Viral - complications; Pneumonia, Viral - drug therapy; Prognosis; QT interval; Risk Factors; SARS-CoV-2; QT interval; azithromycin; COVID‐19; hydroxychloroquine; monitoring
• DOI: 10.1161/JAHA.120.017144
• ISSN: 2047-9980

Background Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected coronavirus disease 2019 (COVID-19). Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods and Results We analyzed a case series of COVID-19-positive/suspected patients admitted between February 1, 2020, and April 4, 2020, who were treated with azithromycin, hydroxychloroquine, or a combination of both drugs. We evaluated baseline and postmedication QT interval (corrected QT interval [QTc]; Bazett) using 12-lead ECGs. Critical QTc prolongation was defined as follows: (1) maximum QTc ≥500 ms (if QRS <120 ms) or QTc ≥550 ms (if QRS ≥120 ms) and (2) QTc increase of ≥60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Of 490 COVID-19-positive/suspected patients, 314 (64%) received either/both drugs and 98 (73 COVID-19 positive and 25 suspected) met study criteria (age, 62±17 years; 61% men). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448±29 ms and increased to 459±36 ms ( =0.005) with medications. Significant prolongation was observed only in men (18±43 ms versus -0.2±28 ms in women; =0.02). A total of 12% of patients reached critical QTc prolongation. Changes in QTc were highest with the combination compared with either drug, with much greater prolongation with combination versus azithromycin (17±39 ms versus 0.5±40 ms; =0.07). No patients manifested torsades de pointes. Conclusions Overall, 12% of patients manifested critical QTc prolongation, and the combination caused greater prolongation than either drug alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients should be carefully assessed.