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

Abstract

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 ECG s. Critical QT c prolongation was defined as follows: (1) maximum QT c ≥500 ms (if QRS <120 ms) or QT c ≥550 ms (if QRS ≥120 ms) and (2) QT c 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 QT c was 448±29 ms and increased to 459±36 ms ( P =0.005) with medications. Significant prolongation was observed only in men (18±43 ms versus −0.2±28 ms in women; P =0.02). A total of 12% of patients reached critical QT c prolongation. Changes in QT c 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; P =0.07). No patients manifested torsades de pointes. Conclusions Overall, 12% of patients manifested critical QT c 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.