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Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring.
J Am Heart Assoc. 2020 06 16; 9(12):e017144.JA

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.

Authors+Show Affiliations

The Smidt Heart Institute, Cedars-Sinai Health System Los Angeles CA.The Smidt Heart Institute, Cedars-Sinai Health System Los Angeles CA.The Smidt Heart Institute, Cedars-Sinai Health System Los Angeles CA.The Smidt Heart Institute, Cedars-Sinai Health System Los Angeles CA.Enterprise Information Systems Data Intelligence Team Cedars-Sinai Health System Los Angeles CA.Enterprise Information Systems Data Intelligence Team Cedars-Sinai Health System Los Angeles CA.The Smidt Heart Institute, Cedars-Sinai Health System Los Angeles CA.The Smidt Heart Institute, Cedars-Sinai Health System Los Angeles CA.The Smidt Heart Institute, Cedars-Sinai Health System Los Angeles CA.The Smidt Heart Institute, Cedars-Sinai Health System Los Angeles CA.The Smidt Heart Institute, Cedars-Sinai Health System Los Angeles CA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32463348

Citation

Ramireddy, Archana, et al. "Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring." Journal of the American Heart Association, vol. 9, no. 12, 2020, pp. e017144.
Ramireddy A, Chugh H, Reinier K, et al. Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring. J Am Heart Assoc. 2020;9(12):e017144.
Ramireddy, A., Chugh, H., Reinier, K., Ebinger, J., Park, E., Thompson, M., Cingolani, E., Cheng, S., Marban, E., Albert, C. M., & Chugh, S. S. (2020). Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring. Journal of the American Heart Association, 9(12), e017144. https://doi.org/10.1161/JAHA.120.017144
Ramireddy A, et al. Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring. J Am Heart Assoc. 2020 06 16;9(12):e017144. PubMed PMID: 32463348.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring. AU - Ramireddy,Archana, AU - Chugh,Harpriya, AU - Reinier,Kyndaron, AU - Ebinger,Joseph, AU - Park,Eunice, AU - Thompson,Michael, AU - Cingolani,Eugenio, AU - Cheng,Susan, AU - Marban,Eduardo, AU - Albert,Christine M, AU - Chugh,Sumeet S, Y1 - 2020/05/28/ PY - 2020/5/29/pubmed PY - 2020/7/7/medline PY - 2020/5/29/entrez KW - COVID‐19 KW - QT interval KW - azithromycin KW - hydroxychloroquine KW - monitoring SP - e017144 EP - e017144 JF - Journal of the American Heart Association JO - J Am Heart Assoc VL - 9 IS - 12 N2 - 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. SN - 2047-9980 UR - https://www.unboundmedicine.com/medline/citation/32463348/Experience_With_Hydroxychloroquine_and_Azithromycin_in_the_Coronavirus_Disease_2019_Pandemic:_Implications_for_QT_Interval_Monitoring_ L2 - https://www.ahajournals.org/doi/10.1161/JAHA.120.017144?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -