In this episode, I’ll discuss advice given by AHA and ACC Presidents on QTc interaction between hydroxychloroquine and azithromycin.
As discussed in episode 488, there is tremendous interest in combining hydroxychloroquine and azithromycin for the treatment of COVID-19 based on a small French observational study.
Performing a risk:benefit analysis is challenging as the French study is far below the level of evidence anyone would usually consider, and the clinical risk of torsades from combining hydroxychloroquine and azithromycin is also unknown.
In a subsequent publication, the authors of the original French study explained how they managed QTc risk:
- Twelve-lead electrocardiograms (ECG) were performed on each patient before treatment and two days after treatment began.
- The treatment was either not started or discontinued when the QTc was greater than 500 ms and a case-by-case decision was made if the QTc was between 460 and 500 ms.
- The treatment was not started when the ECG showed pathological Q waves, left ventricular hypertrophy, or left bundle branch block.
- Any drug potentially prolonging the QT interval was discontinued during treatment.
In the journal Circulation, the presidents of the American Heart Association, American College of Cardiology, and the Heart Rhythm Society have published additional advice on how to handle this interaction.
Their recommendations to minimize arrhythmia risk with this combination are:
- Withhold the drugs in patients with baseline QT prolongation (eg, QTc ≥500 msec) or with known congenital long QT syndrome.
- Monitor cardiac rhythm and QT interval; withdrawal of the drugs if QTc exceeds a preset threshold of 500 msec.
- Correct serum potassium to levels of >4 mEq/L and magnesium to levels of >2 mg/dL.
- Avoid other QTc prolonging agents whenever feasible.
In addition, the Circulation article recognizes that in patients critically ill with COVID-19 infection, frequent caregiver contact may need to be minimized, and optimal electrocardiographic interval and rhythm monitoring may not be possible.
The authors of the original French study also have under publication review a cohort of 1061 patients who were COVID-19 positive and were treated for at least 3 days with hydroxychloroquine plus azithromycin and had follow-up data on day 9 available. A pre-print that has not undergone peer review of this data has been published on the university hospital’s website. The authors state that there was no cardiac toxicity in this cohort of patients. While this is important information, it should be noted that this cohort only represents about one-third of the patients treated at the institution and that any patient who had an arrhythmia in the first 48 hours of treatment would have been excluded from this cohort due to the requirement of receiving 3 days of treatment. Hopefully these questions and more will be answered in the peer-review process.
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