Concerned that the sudden interest in their use for coronavirus could cause fatal heart arrhythmias in a small percentage of what could become millions of users, Mayo Clinic on Wednesday, March 25, issued urgent guidance advising cardiac screening of all who take hydroxychloroquine and chloroquine, malaria drugs touted by President Donald Trump and others as effective for the treatment and prevention of COVID-19.

"We thought it was critical to make people aware how to navigate through and around the sudden cardiac drug risk that does exist with these medications," said Mayo Clinic professor of cardiovascular medicine Dr. Michael Ackerman, "and that's why Mayo Clinic urgently assembled this special article." The article was published in the journal Mayo Clinic Proceedings.

Hydroxychloroquine and the similar drug chloroquine are 80-year old malarial drugs, later used for arthritis, that have shown promise reducing coronavirus counts in the lab but have not shown effectiveness in mice. A handful of reports have claimed the drugs reduce the illness but those studies have been characterized as flawed. Proof of the drugs against coronavirus in the form of positive randomized controlled trials, the accepted measure that a drug is both safe and effective against an illness, do not exist.

Researchers are currently studying the drugs at the University of Minnesota for prevention of COVID-19 after exposure to the virus, but those results will not be available until next year.

The fact of this limited evidence has failed to prevent orders for the drugs from shooting up over 2,000% recently after they were praised by President Trump in a news conference and subsequently on Twitter. Those actions even spurred an elderly couple to ingest a similarly-named aquarium cleaner called chloroquine phosphate, killing an Arizona man in his 60s.

The president's praise of the drug runs against the views of Dr. Anthony S. Fauci, director of the Center for Allergy and Infectious Disease of the Centers for Disease Control, who has called the evidence for chloroquine anecdotal.

The cardiac risks to the drug were not discovered within Mayo Clinic but rather are well-documented within years of adverse event reporting that has been long spelled out on the drug's label. Further limiting its potential for population-wide use, the same label carries a little-noted warning that it can cause suicidal thoughts, emotional instability and nightmares, effects consistent with the side effect known as akathisia.

An estimated 3 million individuals in the United States are believed to possess so-called congenital long QT syndrome, a trait that makes them susceptible to serious cardiac events while taking the medications. Countermeasures are available to mitigate the risk of the adverse events, but they require close surveillance of patients prior to and after going on the drugs, a seemingly tall order for medications being proposed for population-wide use.

"As you look on social media people were starting to use this medication," Ackerman said. "The reaction in the healthcare community ranged from total QT ignorance about this potential side effect, to sort of resignation that the side effect is friendly fire in this war against the coronavirus, to QT drug-induced cardiac arrest hysteria and paranoia. So we really felt we had to get out a message of an ounce of prevention is a pound of cure."

Clearing patients for safe use of chloroquine without countermeasures traditionally involves an ECG, a once-accessible intervention that has become perilous in the age of coronavirus. "The machine has to walk into the patient's room," says Ackerman, "being pushed by a technician who is using up personal protective equipment."

The new Mayo advisory instead directs clinicians to consider a host of risk factors predisposing patients to responding badly to chloroquine. With both types of diabetes, several heart conditions and advanced age all raising red flags, the list is anchored by many of the same factors believed to increase the likelihood of death from coronavirus.

Ackerman sees the potential for safer assessment of chloroquine patients via a newly-approved app developed within Mayo enabling remote determination of ECG. But all of the clinic's advisories appear to come secondary to the central problem of chloroquine in relation to coronavirus: the nation has embarked on a mad rush to stock up on a drug with known risks, and unknown rewards.

"If we don't know about this side effect, or are not respecting it as we begin potentially dosing hundreds of thousands or even millions with this medication," Ackerman says, "this side effect is going to claim lives."

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