Hydroxychloroquine in combination with azithromycin and abnormal cardiac rhythm in COVID-19 patients

A new study shows that the first admired drug combination for COVID-19-hydroxychloroquine and chloroquine in combination with azithromycin may lead to abnormal and life-threatening heart rhythms. In patients admitted with a novel coronavirus infection or SARS CoV-2, this combination may increase the QT interval to be detectable by ECG. A study titled “Risk of QT interval prolongation (COVID-19) associated with the use of hydroxychloroquine with or without azithromycin in hospitalized patients with coronavirus 2019 positive” was published in the latest issue of the journal JAMA Cardiology.

What was this study about?

The study, led by Dr. Howard S. Gold of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, was essentially observatory. The first author of the study was Nicholas J. Merclo. The study’s authors write that the drug combination was originally advertised as a treatment for people diagnosed with COVID-19-related pneumonia. The main purpose of the study was to “characterize the risk and extent of QT prolongation in COVID-19 patients associated with the use of hydroxychloroquine with or without azithromycin.” They measured the correct QT interval in study participants.

ECG signaling QT interval 3d illustration. Image credit: sciencepics / Shutterstock

what did you do?

This observational cohort study was conducted at a tertiary care center in Boston, Massachusetts. Participants were patients with at least one detection of a viral infection. One of their nasopharyngeal swabs was positive for at least the SARS CoV-2 polymerase chain reaction test (PCR test). All of these participants were clinically diagnosed with pneumonia and were on hydroxychloroquine for at least one day during one day.^st March and July 2020^Th April 2020.

The patient’s electrocardiogram (ECG) record was measured. The ECG records several waves of P, Q, R, S, and T. The distance between the waves is measured. The two important waves measured include the PR interval and the QT interval. Other potential side effects of the drug or its combination were also recorded.

What did you find?

The study included a total of 90 participants who received hydroxychloroquine. Of these, 53 received a combination of azithromycin. Among participants, 48.9% (44 by number) were female, with an average body mass index of 31.5 for all participants. Of the patients, 53.3% had hypertension (48 cases) and 28.9% had diabetes (26 cases). These two conditions were most commonly found among patients.

The results revealed a median baseline QTc of 455 (430-474) ms at the start of the study. The median QTc for hydroxychloroquine is 473 ms (range 454 ms to 487 ms). Among those related to hydroxychloroquine and azithromycin, the median QTc was 442 ms (range 427 ms to 461 ms). The post-administration prolongation of the drug combination was found to be statistically significant.

The researchers found that patients with concomitant azithromycin had greater changes in the median QT interval (quartile range) (23 [10-40] (Milliseconds) compared to those given hydroxychloroquine alone (5.5 [−15.5 to 34.25] millisecond. “

In some patients, severe cardiac arrhythmias were noted. Of the participants, 7 (19%) who received only hydroxychloroquine had an extended QTc interval of ≥500 ms. Three patients differed by 60 ms from baseline. In addition, 21% of patients receiving azithromycin (11 of 53 who received combination therapy) had a QTc interval of more than 500 ms. Between 13% (7 out of 53 participants) the change was over 60 ms.

The researchers also noted that patients who received loop diuretics such as furosemide were at increased risk of QTc interval prolongation compared to patients who did not receive such drugs. The odds ratio of developing an extended QTc among those who received these combinations was 3.38. Risk increased at odds ratios of baseline QTc intervals of 450 ms or more (odds ratio of 7.11).

One of the participants developed a severe cardiac rhythm abnormality called torsades de pointes. Ten patients had to discontinue hydroxychloroquine due to side effects such as nausea and hypoglycemia.

Study conclusions and importance

The researchers concluded that participants diagnosed with COVID-19 pneumonia receiving hydroxychloroquine were at increased risk of QTc prolongation. This risk was increased by the addition of azithromycin. They also write that one of their cases in Torsades de Pointes was the first such case to be reported with this drug combination. They called for more detailed studies to assess the risks and benefits of using these drugs among patients diagnosed with COVID-19. They recommended that all patients require “regular ECG and electrolyte monitoring” during treatment.

“When considering hydroxychloroquine and azithromycin, clinicians must carefully weigh the risks and benefits while closely monitoring the use of QTc and concomitant medications.”

Accompanying editorial

To Accompanying editorial Talked about the complexity of decision making in the treatment of patients with COVID-19, entitled “Hydroxychloroquine, Coronavirus Disease 2019, and QT Prolongation,” by Robert O. Bonow, Adrian F. Hernandez, and Mintu Turakhia.

They emphasize that there is no proven treatment strategy for this infection. “The lack of robust clinical trial evidence forces clinicians to consider all options based on preclinical and small observational studies. Often exacerbated by severe pneumonia pain. In a setting that hurt the heart of a patient who is … “

The authors noted that hydroxychloroquine could prolong the QT interval by “blocking intracellular potassium currents.” Azithromycin has a similar risk. They call these findings “welcome and important.” However, in an intensive care setting, it is easy to monitor a patient’s electrocardiogram and the drug can be used if it proves beneficial.

The authors note that there are two trials in progress. (ISRCTN50189673) “. These provide a detailed safety profile for the drug.

“Until then, decisions about how to treat this disease remain based on clinical judgment, ideally in the context of enrolling patients in clinical trials and providing definitive answers.” I concluded.