Feature | Coronavirus (COVID-19) | May 27, 2020

WHO Database Shows Serious Health Impact of Hydroxychloroquine and Azithromycin Being Used to Treat COVID-19

Circulation report shows 167,000 adverse event reports for these drugs over last 50 years

WHO Database Shows Serious Health Impact of Hydroxychloroquine and Azithromycin Being Used to Treat COVID-19. #COVID19 #SARScov2 #Hydroxychloroquine

May 27, 2020 — Two of the front-line drugs being used to treat COVID-19 (SARS-CoV-2) patients are hydroxychloroquine and azithromycin, but a new study shows these drugs in combination may pose a serious impact on the cardiovascular system and are a potentially lethal combination. Both drugs cause QT-prolongation. Additional information is now available from a large analysis of a World Health Organization (WHO) database on adverse drug reactions hoping back to 1967, published May 22 in Circulation, the flagship journal of the American Heart Association (AHA).

The study, “Cardiovascular Toxicities Associated with Hydroxychloroquine and Azithromycin: An Analysis of the World Health Organization Pharmacovigilance Database,” is an observational, retrospective meta-analysis of a WHO database encompassing more than 21 million adverse event case reports across all medication classes from more than 130 countries between Nov. 14, 1967, and March 1, 2020, mainly before the COVID-19 pandemic.

The study compared cardiovascular adverse drug reactions (CV-ADRs) in patients who received hydroxychloroquine, azithromycin, or the combination of both medications with all other cardiovascular medications in the database. Hydroxychloroquine and azithromycin, alone or in combination, have been proposed for treatment of COVID-19 patients.

From the more than 21 million case reports of adverse drug reactions, researchers extracted case reports for hydroxychloroquine and azithromycin, alone or in combination:

   • 76,822 adverse event reports were associated with hydroxychloroquine alone, and in 28.4 percent of those cases (21,808), hydroxychloroquine was suspected to be associated with the adverse event. 
   • 89,692 adverse event reports were associated with azithromycin alone, and in 60.8% of those cases (54,533), azithromycin was suspected to be associated with the adverse event.
   • 607 adverse event reports reported were associated with the combination of both medications.

The analysis of the WHO database cases found:

   • There was a statistically significant greater reporting of prolonged-QT (LQT) and/or ventricular tachycardia including Torsades-de-Pointes (TdP/VT) for each medicine individually in the suspected cases compared to all other medications.
   • Hydroxychloroquine was also significantly associated with the development of conduction disorders (atrioventricular block and bundle branch block) and heart failure.
   • Azithromycin monotherapy was associated with greater reporting of LQT and/or TdP/VT than hydroxychloroquine alone (0.8% vs. 0.3%, respectively).
The combination of hydroxychloroquine and azithromycin was associated with a greater reporting of LQT and/or TdP/VT than either medication alone (0.6% vs. 1.5%, respectively).
   • No other cardiovascular adverse events, including cardiac ischemia and myocarditis, were significantly associated with these medicines.
   • The proportion of cases that resulted in death for TdP/VT cases was 8.4% (7/83) with hydroxychloroquine, and 20.2% (52/257) with azithromycin, vs. 0% (0/53) and 5.4% (12/223) for LQT without TdP/VT with hydroxychloroquine and azithromycin, respectively.

The researchers conclude, “reports of potentially lethal acute cardiac pro-arrhythmogenic effects have been described mainly with azithromycin, but also with hydroxychloroquine. Their combination yielded an even stronger signal. Hydroxychloroquine was also associated with potentially lethal heart failure when exposure was prolonged over several months. While the absolute case numbers were low, these CV-ADRs are important to bear in mind in the setting of COVID-19 patients who may present with additional risk factors for LQT/TdP including inflammation with elevated interleukin-6, hypokalemia, numerous interacting medications, bradycardia and higher hydroxychloroquine doses.”

As detailed in the American Heart Association’s joint guidance from April 8, 2020, “Considerations for Drug Interactions on QTc in Exploratory COVID-19 (Coronavirus Disease 2019) Treatment,” both medications are known to have potentially serious complications for people with cardiovascular disease.[2] These complications include increased risk of sudden death, and the effect on the QT interval or arrhythmia risk of these two medications combined has not been studied.

“Hydroxychloroquine and azithromycin have increased cardiovascular toxicity, should not be administered outside of a clinical trial, and require close additional cardiovascular monitoring and treatment,” said Mariell Jessup, M.D., FAHA, chief science and medical officer of the AHA.

The authors of the study are Joe-Elie Salem, M.D., Ph.D.; Lee S. Nguyen, M.D.; Charles Dolladille, M.D.; Milou-Daniel Drici, M.D., Ph.D.; Charlotte Fenioux, M.D.; Joachim Alexandre, M.D., Ph.D.; Jean-Paul Mira, M.D., Ph.D.; Javid J. Moslehi, M.D.; Dan M. Roden, M.D.; and Christian Funck-Brentano, M.D., Ph.D. The authors report no disclosures related to this study, and no external funding sources for this study.

Additional Hydroxychloroquine and Azithromycin COVID-19 Content:

VIDEO: Why QT-prolongation Occurs in COVID-19 Patients on Hydroxychloroquine — Interview with Andrew Krahn, M.D.

All COVID-19 research published in AHA journals

AHA COVID-19 information for healthcare professionals and researchers

VIDEO: Overview of Hydroxychloroquine and FDA Warning in its use to Treat COVID-19 — Interview with Marianne Pop, Pharm.D.

 

FDA Reports of Deaths and Injuries From Use of Antimalarial hydroxychloroquine in COVID-19 Patients

AHA, ACC, HRS Caution Use of COVID-19 Therapies Hydroxychloroquine and Azithromycin in Cardiac Patients

COVID-19 Hydroxychloroquine Treatment Brings Prolonged QT Arrhythmia Issues 

 

VIDEO: Cardiologists Manage Trial Testing if Hydroxychloroquine Protects Clinicians From COVID-19

First Large-scale U.S. Study on Hydroxychloroquine COVID-19 Prophylaxis Begins in Detroit

 

 

References:

1. Lee S. Nguyen, Charles Dolladille, Milou-Daniel Drici, et al. Cardiovascular Toxicities Associated with Hydroxychloroquine and Azithromycin: An Analysis of the World Health Organization Pharmacovigilance Database. Circulation. Originally Published online 22 May 2020. https://doi.org/10.1161/CIRCULATIONAHA.120.048238.

2. Dan M. Roden, Robert A. Harrington, Athena Poppas, and Andrea M. Russo. Considerations for Drug Interactions on QTc in Exploratory COVID-19 (Coronavirus Disease 2019) Treatment. Circulation. Published online 8 Apr 2020. doi.org/10.1161/CIRCULATIONAHA.120.047521.

 


Related Content

News | AHA

February 9, 2024 — Injection of a substance to block an artery feeding the dura (protective sack around the brain) — ...

Home February 09, 2024
Home
News | AHA

February 8, 2024 — The American Heart Association (AHA), currently celebrating its centennial year, announced that it is ...

Home February 08, 2024
Home
News | AHA

February 8, 2024 — The latest late-breaking science from the second day of the American Stroke Association’s ...

Home February 08, 2024
Home
News | AHA

February 7, 2024 — According to results from a multi-center trial in the United States, called Zero Degree Head ...

Home February 07, 2024
Home
News | AHA

February 7, 2024 — Researchers presenting preliminary late-breaking science presented on the first day of the American ...

Home February 07, 2024
Home
News | AHA

February 7, 2024 — Eleven scientists leading the way in stroke research will be recognized during the American Stroke ...

Home February 07, 2024
Home
News | AHA

January 23, 2024 — Focused on delivering the latest scientific advancements and new treatments in cerebrovascular ...

Home January 22, 2024
Home
News | AHA

January 18, 2024 — A new American Heart Association (AHA) policy statement examines the history of structural racism ...

Home January 18, 2024
Home
News | AHA

November 13, 2023 — Vektor Medical, a pioneer in non-invasive arrhythmia analysis technology, is proud to highlight two ...

Home November 13, 2023
Home
News | AHA

November 11, 2023 — Results of a randomized trial presented today at the American Heart Association’s Scientific ...

Home November 11, 2023
Home
Subscribe Now