It’s out there and used for lupus and rheumatoid arthritis. We are in April 2020 , the pandemic is in force, and some people are getting it for Covid-19 infection.

It’s not just that it is hard to be sure how well hydroxychloroquine works against the virus.

The evidence is speculative, but if it might work, the argument is strong to try it when desperate measures are called for. The consideration of side effects seems to be a lower priority. When given to a small number of people who are at very high risk of dying from Covid-19 the potential for harm seems to be dwarfed by the risks that come from the viral infection itself.

The problem of accounting for side effects is more important when you start talking about giving it to a great number of people who have a much lower risk of dying from the Covid-19 infection.

If lower risk people take hydroxychloroquine in large numbers the risk of side effect that can cost lives stays the same but the chance of saving lives goes down. The increasing number of lives lost from side effects can start to be substantial compared to the lives saved by the treatment.

So it is increasingly important to know what these risks and benefits are when more and more people take the drug.

The concerning and potentially life threatening side effect associated with hydroxychloroquine is called “Long QT”. During heart contraction electrical current discharges into each heart cell. After the contraction the heart muscle relaxes and the battery recharges. A “Long QT” occurs when the recharge takes longer than normal. The problem with a “Long QT” is that it sets up the circumstances for the electrical currents to be confused. Heart muscle cells can start discharging when they should be charging. This can lead to total electrical chaos in the heart, a condition called ventricular fibrillation. When a ventricle fibrillates, it does not pump blood, and you die. So ventricular fibrillation is the most common cause of cardiac arrest and “sudden death”, and “Long QT” is a cause of ventricular fibrillation.

A “Long QT” refers to a time interval on the electrocardiogram. The only way to diagnose “Long QT” is to record an electrocardiogram (ECG).

From experience giving hydroxychloroquine for conditions like arthritis, we know that only a few percent of people taking it will get a long QT interval. Only a few percent of those will have a problem with heart rhythm if the QT interval is long but the duration of therapy is short.

But if millions of people are taking hydroxychloroquine problems emerge.

People will die of cardiac arrest who would not have died of covid-19.

How can you monitor the ECGs of so many people to see if the QT interval becomes a problem?

Other medications have been placed in widespread use and only later was it discovered that people were dying from long QT related sudden death. It is appropriate to give some consideration to this issue now as well.

The American College of Cardiology and the Heart Rhythm Society have published a statement giving guidance how the investigation of the use of hydroxychloroquine for use in Covid-19 infection should be performed. There are clearly people who have a long QT interval or have other conditions or therapies that place them at risk of “Long QT” who should not get the drug.  Studies should include ECG monitoring to determine how much danger is presented by the QT lengthening effect of the drug. Account needs to be taken regarding how much resource will be needed to monitor the QT prolonging effect of hydroxychloroquine if given to large numbers of people. It is acknowledged that innovative approaches to ECG monitoring like wearable technology can potentially be useful.

Treatments for a disease like Covid-19 are best tested for effectiveness and safety by randomizing people to the therapy or no therapy.

The only randomized study of hydroxychloroquine so far completed included 64 patients from Wuhan University who were moderately symptomatic. Those randomized to hydroxychloroquine  and had improved symptoms and shorter hospital stays. This small of a study cannot tell how powerful the treatment is to saves lives.

There are larger randomized trials currently enrolling patients that are symptomatic with Covid-19. There are also trials testing whether hydroxychloroquine can help prevent people from getting the virus after exposure.

There are no drugs or other therapeutics approved by the US Food and Drug Administration to prevent or treat COVID-19. The practice in major hospitals in the US is currently to offer symptomatic hospitalized patients with Covid-19 the option of enrolling in a clinical trial of hydroxychloroquine or other therapies. If they are unwilling or unable to enter a study, hydroxychloroquine is used on a case by case basis.

“Off label use” is the term used to describe the use of medication that the FDA has not approved for a particular condition. “Off label use” of hydroxychloroquine in a hospital at the direction of doctors experienced in the treatment of Covid-19 infection is one thing, trying it yourself at home is another. We need to know whether hydroxychloroquine is helpful and in whom. We also need to know at what risks it might present to different populations, whether monitoring may be needed to reduce the risks, and what kind of monitoring that might be.

The medical community is working hard and fast toward answering these questions with a speed appropriate to the urgency of the situation.

We all hope that this, or other therapies, will quickly come on board to fight this terrible disease.

J Thomas Svinarich MD FACC FHRS

Colorado Center for Functional Medicine

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