A new study shows that a combination of drugs that were initially praised for COVID-19 – Hydroxychloroquine and Chloroquine combined with azithromycin, can cause abnormal and life-threatening heart rhythms. In patients who are hospitalized with new coronavirus infections or SARS CoV-2, this combination can cause prolonged QT intervals as can be detected on an ECG. The study, entitled, “Risks of QT Interval Extensions Related to the Use of Hydroxychloroquine With or Without Azithromycin Concurrent Among Inpatients Who Test Positive for Coronavirus 2019 (COVID-19),” is published in the latest issue of the journal JAMA Cardiology.
What is this research about?
Research led by Dr. Howard S. Gold of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston is basically observational research. The first author of this study was Nicholas J. Mercuro. The study authors wrote that this combination of drugs was initially cited as a treatment for people who had been diagnosed with COVID-19-associated pneumonia. The main objective of this study was to “characterize the risk and extent of QT prolongation in patients with COVID-19 in connection with their use of hydroxychloroquine with or without concurrent azithromycin.” They measured the correct QT interval for study participants.
QT interval in 3d illustration of ECG signaling. Image Credit: sciencepics / Shutterstock
What was done
This observational cohort study was conducted at a tertiary care center in Boston, Massachusetts. Participants are patients who have been detected at least once with a viral infection. One of their nasopharyngeal swabs has at least tested positive in the polymerase chain reaction test (PCR test) for SARS CoV-2. All of these participants were clinically diagnosed with pneumonia and had received at least 1 day of hydroxichloroquine between 1st March 2020 and 7th April 2020.
Electrocardiogram (ECG) records of patients were measured. On an ECG, several waves are recorded – P, Q, R, S, and T. Intervals between waves are measured. Two significant waves measured include the PR interval and the QT interval. Other potential side effects of the drug or its combination are also noted.
What was found?
For this study, a total of 90 participants who received hydroxychloroquine were included. Of these, 53 have received azithromycin in combination. Among participants, 48.9 percent (total 44) were women, and the average body mass index was 31.5 for all participants. Among patients, 53.3 percent had high blood pressure (48 patients), and 28.9 percent had diabetes mellitus (26 patients). Both of these conditions are most often found among patients.
The results revealed that at the start of the study, the median initial QTc was 455 (430-474) milliseconds. The median QTc for those using hydroxychloroquine is 473 milliseconds (ranging from 454 milliseconds to 487 milliseconds). Among those using hydroxychloroquine and azithromycin, the median QTc was 442 milliseconds (ranging from 427 milliseconds to 461 milliseconds). The extension after administration of a combination of drugs was found to be statistically significant.
The researchers wrote, “Those who received concurrent azithromycin had a greater median (interquartile range) in the QT interval (23). [10-40] milliseconds) compared to those who received hydroxychloroquine alone (5.5 [−15.5 to 34.25] millisecond. “
Serious heart rhythm arrhythmias have been found in some patients. Of the participants, seven (19 percent) who had received hydroxychloroquine alone had a QTc interval that lasted 500 milliseconds or more. Three of the patients had a difference of 60 milliseconds from the start. Among those who received azithromycin, 21 percent (11 of 53 who received the combination) had a QTc interval of more than 500 milliseconds. The change is 60 milliseconds or more between 13 percent (7 out of 53 participants).
The researchers also noted that patients given loop diuretics such as furosemide had a higher risk of extending the QTc interval compared to those who did not receive the drug. The chance ratio was found by the researchers, developing a prolonged QTc among those who received this combination was 3.38. Risk is increased for those who have an initial QTc interval of 450 milliseconds or more (odds ratio 7.11).
One participant developed a severe heart rhythm abnormality called torsades de pointes. Ten patients had to stop hydroxychloroquine due to drug side effects, including nausea and low blood sugar.
Conclusions and importance of research
The researchers concluded that participants who were diagnosed with COVID-19 pneumonia given hydroxychloroquine were at a higher risk for prolongation of QTc. This risk increases with the addition of azithromycin. They also wrote that one of their cases of torsades de pointes was the first case reported with this combination of drugs. They called for more detailed research to assess the risks and benefits of using this drug among patients diagnosed with COVID-19. They recommend that all patients require “routine electrocardiogram, and electrolyte monitoring” during therapy.
The authors write, “Doctors must carefully consider the risks and benefits when considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concurrent drug use.”
In accompanying editorial titled “Hydroxychloroquine, Coronavirus Disease 2019, and QT Prolongation,” by Robert O. Bonow, Adrian F. Hernandez, and Mintu Turakhia talk about the complexity of decision making when treating COVID-19 patients.
They emphasize the fact that there is no proven treatment strategy for this infection. They wrote, “Lacking strong trial evidence, doctors are forced to consider all options based on preclinical and small observational studies, often in the heartbreaking arrangement of patients who worsen in the upheaval of severe pneumonia …”
The authors write that hydroxychloroquine is able to extend the QT interval due to “inadequate cellular potassium flow.” Azithromycin also carries a similar risk. They called this finding “welcome and important.” They added, however, that in intensive care settings, it was easy to monitor the patient’s ECG, and if proven useful, the drug could be used.
The authors say that there are two ongoing trials – “Results Associated with COVID-19 Treated with Hydroxychloroquine Among Inpatients With Symptoms of Disease (ORCHID) (NCT04332991) 12 and Randomized evaluation of COVID-19 Therapy (RECOVERY) (ISRCTN50189673) ) “. This will provide a detailed drug safety profile.
They concluded, “Until then, treatment decisions for this disease will remain based on clinical judgment and, ideally, in the context of enrolling patients in clinical trials to provide definitive answers.”
to request modification Contact us at Here or [email protected]