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

J Am Heart Assoc. 2020 Jun 16;9(12):e017144. doi: 10.1161/JAHA.120.017144. Epub 2020 May 28.

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 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 (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 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; P=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.

Keywords: COVID‐19; QT interval; azithromycin; hydroxychloroquine; monitoring.

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Antimalarials / therapeutic use
  • Azithromycin / therapeutic use*
  • Betacoronavirus*
  • Coronavirus Infections / complications
  • Coronavirus Infections / drug therapy*
  • Drug Therapy, Combination
  • Electrocardiography / drug effects*
  • Female
  • Humans
  • Hydroxychloroquine / therapeutic use*
  • Long QT Syndrome / chemically induced*
  • Long QT Syndrome / physiopathology
  • Male
  • Middle Aged
  • Pandemics*
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / drug therapy*
  • Prognosis
  • Risk Factors

Substances

  • Anti-Bacterial Agents
  • Antimalarials
  • Hydroxychloroquine
  • Azithromycin

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2