COVID-19: White House Pushes Unproven Drugs—Risk of Arrhythmias and Sudden Death

by Steve S. Ryan

Note: I have already written about the risk of COVID-19 for patients with A-Fib (and other cardiovascular diseases). See my post: COVID-19 Virus: Higher Risk for A-Fib Patients.

In recent coronavirus pandemic press conferences, President Donald Trump has repeatedly advocated the use of the drugs hydroxychloroquine (HCQ) and azithromycin (Z-Pak) to treat the COVID-19 virus.

He often says, “What have you got to lose?” About treating patients, he also said these drugs can “help them, but it’s not going to hurt them.” (Really?)

Hydroxychloroquine & Azithromycin Danger―“What Have You Got to Lose?”

The drugs hydroxychloroquine and azithromycin are currently gaining attention as potential treatments for COVID-19. Hydroxychloroquine sulphate (Plaquenil) is an antimalarial medication. Azithromycin (Z-Pak) is an antibiotic. (Antibiotics in general are ineffective against viruses.)

Each has potential serious implications for people with existing cardiovascular disease.

Contrary to Mr. Trump’s statements, you do have a lot to lose. Medical groups warn that it’s dangerous to be hawking unproven remedies.

Recently, three U.S. heart societies published a joint statement to detail critical cardiovascular considerations in the use of hydroxychloroquine and azithromycin for the treatment of COVID-19.

According to the “Guidance from the American Heart Association, the American College of Cardiology and the Heart Rhythm Society”:

Complications include severe electrical irregularities in the heart such as arrythmia (irregular heartbeat), polymorphic ventricular tachycardia (including Torsade de Pointes) and long QT syndrome, and increased risk of sudden death.

The effect on QT or arrhythmia of these two medications combined has not been studied.

With these increased dangers in mind, we must not take unnecessary (or foolish) risks in the rush to find a treatment or cure for COVID-19.

What We Know So Far About These Drugs and COVID-19

SMALL CHINA STUDY SHOWS HCQ IS EFFECTIVE

A small randomized study (62 patients) in China of Hydroxychloroquine (HCQ) alone showed that it did improve —shorter time to clinical recovery (1 day) and improved pneumonia. HCQ was only used for around 5 days.

According to the author, Dr. Zhan Zhang of Wuhan University, China, “short-term application of HCQ is relatively safe.”

It may help prevent or treat infection by interfering with angiotensin-converting enzyme 2 receptors, which the COVID-19 virus uses for cell entry. As Dr. Zhang concluded, “considering that there is no better option at present, it is a promising practice to apply HCQ to COVID-19 under reasonable management.”

DOES COMBINING THESE DRUGS WORK?

The effect of combining these two medications has not been studied with regards to arrhythmia and QT interval.

According to Dr. Andrea M. Russo, president of the Heart Rhythm Society, “Given the potential for increased risks related to combinations of medications that prolong the QT interval, we urge careful consideration…”

There is very limited data evaluating the safety of this combination therapy.

PRELIMINARY STUDY: HCQ AND Z-PAK IN COMBINATION

In a small, not yet published study by well-known electrophysiologists (including Larry Chinitz of NYU Langone), 84 adults with SARS-CoV-2 (COVID-19) were treated with the drug combination Hydroxychloroquine(HCQ)/Azithromycin(Z-Pak).

In these patients, this drug combination affected the heart’s QT interval (electrical properties of the heart).

ECG waveform diagram showing the QT interval.

In 30% of these patients, QTc increased by greater than 40ms. In 11%, QTc increased to greater than 500 ms, which means they are at high risk for arrhythmia. (“QTc” is the QT interval corrected for heart rate extremes.)

For most people, those odds of developing or worsening heart arrhythmias from taking these drugs are unacceptable.

(QT interval is a measurement made by an electrogram used to assess some of the electrical properties of the heart. To learn more about the QT interval, see my article, “Understanding the EKG Signal“.)

Bottom Line for A-Fib Patients

“While these medications may work against COVID-19 individually or in combination, we recommend caution with these medications for patients with existing cardiovascular disease.

The urgency of COVID-19 must not diminish the scientific rigor with which we approach COVID-19 treatment.”  ̶ Robert A. Harrington, M.D., FAHA, president of the American Heart Association

Editor’s Comments

It would be terrible if people started taking HCQ (hydroxychloroquine) and Z-Pak (azithromycin) as a treatment for COVID-19, then developed arrhythmias like A-Fib/Flutter, or even worse Torsades de Pointes and long QT syndrome which increase the risk of sudden death.

COVID-19 Patients With Arrhythmias: In a recent report from Wuhan, China, 16.7% of people who came to the hospital and 44.4% of ICU patients with COVID-19 had arrhythmias.

The last thing you would want to do is to give these patients drugs that would start, increase, or worsen arrhythmias.

When three major U.S. heart organizations warn about taking these drugs, we should take notice.

In the China limited study, HCQ was only used for a short period of time (around 5 days). Is that enough of a dosage to affect arrhythmias? We don’t know. That’s why it’s imperative to do clinical studies before recommending these drugs.

HCQ/Z-Pak Could Kill You or Endanger Your Health Forever: The preliminary preprint study cited above, though not yet peer-reviewed and evaluated, nevertheless raises significant red flags, particularly for people with A-Fib/Flutter.

Most people do recover from COVID-19. But the HCQ/Z-Pak combination not only increases the risk of sudden death, it may saddle people with A-Fib/Flutter for the rest of their lives.

Preliminary studies (and common sense) show that this drug combination could kill you or seriously endanger your health forever.

“What Have You Got to Lose?” A lot, Mr. President!  In spite of what Mr. Trump advocates, the HCQ/Z-Pak drug combination needs to be clinically tested first before it’s prescribed for patients.

Update: April 15, 2020, 1 AM:

The Negative Data Keeps Coming: In Brazil, a small trial of higher-dose chloroquine plus the antibiotic azithromycin for COVOD-19 had to be halted after a quarter of recipients developed long QT intervals and a trend for higher mortality. 11 of these patients died (13.5%).

France reported 43 cases of heart incidents with the experimental drug hydroxychloroquine.

In the U.S. the OHDSI-COVID-19 consortium reports serious adverse events emerged when rheumatoid arthritis (RA) patients took azithromycin at the same time as hydroxychloroquine (HCQ). The HCQ-azithromycin combination was associated with increased risk of cardiovascular mortality, chest pain/angina and heart failure.

Update: APRIL 25, 2020:

More Negative Reports from the FDA:

The FDA issued a drug safety communication (April 24, 2020) warning of the known risk of potentially fatal cardiac rhythm problems with the use of hydroxychloroquine (NCQ, Plaquenil) and chloroquine. In the FDA’s adverse event database, these drugs for treating COVID-19 have “included QT interval prolongation, ventricular tachycardia and ventricular fibrillation, and in some cases death.” (Unlike Atrial Fibrillation, Ventricular Fibrillation usually kills you.)

Adverse events have occurred for NCQ and chloroquine, both alone and when combined with the antibiotic azithromycin.

Most of the 84 consequitive patients with COVID-19 treated with a 5-day course of HCQ and azithromycin at NYU Langone Health in New York City developed prolonged QTc. In nine patients (11%) QTc went above the 500 ms mark that spells high risk of malignant arrhythmia and succen cardiac death. Five of these patients had been admitted with a norrmal QT interval.