Doctors are cautioning that using hydroxychloroquine to treat coronavirus may be dangerous after more than 90 percent of COVID-19 patients in two studies of the drug developed signs of dangerous heart arrhythmias.
If heart rhythms remain irregular for too long, it can trigger heart attack and stroke.
Heart arrhythmias are a known and potentially life-threatening side effect of the malaria and lupus drug touted by Trump, so researchers in the US and France carefully monitored 90 and 40 patients, respectively, for them.
Each found that more than 90 percent of coronavirus patients in ICUs showed longer-than-normal delays between heartbeats, a worrisome sign that the drug might be disrupting their cardiac function.
In an accompanying editorial in JAMA Cardiology, Northwestern University cardiologist Dr Robert Bonow warned that once these signs emerge, ‘allowing treatment beyond these limits…in patients with COVID-10 should not be recommended unless there are clear benefits associated with anti-inflammatory or antiviral effects that are yet to be clinically demonstrated.’
Hydroxychloroquine may raise the risks of dangerous arrhythmias that can trigger heart attacks in more than 90% of coronavirus patients treated with the drug, two studies suggest (file)
Although early studies suggested it could help coronavirus patients, heart arrhythmias are a known and dangerous side effect of the malaria and lupus drug
Doctors, patients and President Trump looked to hydroxychloroquine with optimism after a French study suggested it had drastically improved survival rates and recovery times for coronavirus patients.
The FDA gave emergency use authorization for doctors to try the drug for US coronavirus patients, although the journal that published the French study later said the research did not meet the publication’s standards.
Nonetheless, trials, off-label uses, hoarding and internet searches for hydroxychloroquine surged in the US and around the world.
‘Among possible therapies, hydroxychloroquine has been advocated and even politicized as a promising therapy because of its anti-inflammatory and potential antiviral properties,’ Dr Bonow noted in his editorial.
‘The drug, known for its immunosuppressive and antimalarial effects, has risen to the top of many treatment algorithms alone or in combination with azithromycin.’
In lab studies, the drug, approved by the Food and Drug Administration (FDA) in 1955, appeared to have antiviral qualities, and the possible ability to bat back out of control inflammation thought responsible for the deaths of many coronavirus patients.
But the drug is not without its own dangers.
QT intervals measure the time between when the heart’s ventricular muscle contracts then relaxes. Prolonged QT intervals are a sign of dangerous heart arrhythmias. Many coronavirus patients in the Boston trial had longer QT intervals after staring the drug especially in combination with azithromycin, graphs from the study show
Although it’s used to treat malaria and autoimmune conditions like lupus and rheumatoid arthritis, hydroxychloroquine may throw off the process that makes the heart beat in time.
One trial in Brazil was stopped short because so many of the enrolled coronavirus patients being treated with the drug developed these arrhythmias.
In order to try to quantify when, why and how frequently this was happening, researchers at Massachusetts General Hospital in the US and the University of Lyon in France closely monitored so-called QT intervals in critical coronavirus patients treated with hydroxychloroquine.
The QT interval measures, in effect, the time that passes between when the heart’s ventricular muscle contracts and then relaxes.
When this interval becomes too long, the patient has developed a dangerous form of heart arrhythmia, called atrial fibrillation – the same condition that Apple Watches have been hailed for catching, saving the lives of their wearers.
It’s also one of the leading reasons that patients are advised to stop taking a given medication.
A normal QT interval lasts between 400 and 440 milliseconds (men have shorter QT intervals than women).
In the French study, a quarter of the patients had QT intervals that lasted 60 milliseconds too long or more and 18 percent had intervals lasting 500 milliseconds or longer.
Out of the 40 patients in the study, 37, or 93 percent, experienced prolonged QT levels.
In the Mass Gen study, 20% of the 90 patients treated developed QT levels that lasted or exceeded 500 milliseconds. Of those, 30 were being treated in ICUs, suggesting they were already in fragile conditions.
Taken together, more than 90 percent of the combined 130 patients had longer-than-normal QT intervals. Some developed such dangerous heart arrhythmias that treatment was stopped early.
It’s particularly worrisome now that doctors think coronavirus may attack the heart and cardiovascular system, either by infecting the tissue (called cardiomopathy), triggering clots by damaging blood vessels or via the inflammation the virus causes.
Dr Bonow notes that acutely ill patients like most of those treated in the two studies may be at greater risk of heart arrythmias due to other factors.
He also writes that it’s possible that in some scenarios the potential benefit of hydroxychloroquine – once established by further studies – may outweigh the risk of arrhythmias.
That sentiment is reflected on the American College of Cardiology’s website about the experimental use of hydroxychloroquine to treat COVID-19 patients: ‘While QT-prolonging medication use has been associated with increased risk of death, this risk may be smaller than the potential benefit from treatment of COVID-19 for some patients.
‘Currently, there is hope for benefit from hydroxychloroquine, yet there is little evidence. That is likely to rapidly change, given many pending clinical studies.’
In his editorial, Dr Bonow does not advise that clinical trials of the drug stop, but warns they should proceed with caution.
‘Understanding whether this risk is worth taking in the absence of evidence of therapeutic efficacy creates a knowledge gap that needs to be addressed,’ he writes.
‘Whether signals of potential benefit outweigh signals of harm is unknown until well controlled clinical trials are completed for the treatment or prevention of COVID-19 infections.’
He adds that availability of alternative potential treatments will also play into this calculus, which may be altered by the encouraging early results of trials of remdesivir announced this week.
HYDROXYCHLOROQUINE DISAPPOINTS IN NEW YORK TRIAL OF 600 CORONAVIRUS PATIENTS
It comes after further disappointing preliminary data from a hydroxychloroquine trial in New York.
Patients treated with hydroxychloroquine have no better chance of survival than those who don’t receive the drug hailed by Trump as a ‘game-changer,’ results of the trial suggested.
‘I think from the review that I heard basically it was not seen as a positive, not seen as a negative,’ said Governor Andrew Cuomo during CNN’s coronavirus town hall.
Ultimately, the study, conducted by SUNY at Albany, is intended to involved some 4,000 coronavirus patients, but the preliminary results are from a sample of 600 patients.
Survival rates were no better among the group treated with the experimental drug than among those who got the standard supportive care, including oxygen, IV fluids and, if necessary, mechanical ventilation.
President Trump has touted hydroxychloroquine as a ‘game-changer’ for treating COVID-19 – despite the fact the drug hasn’t been proven effective
Last Friday, shortly after preliminary results were reported, the Food and Drug Administration (FDA) formally warned against using the drug outside of hospitals due to the risk that it could cause heart arrhythmias.
It wasa major blow to President Trump, who has sung the praises of the drug, as well as to the global search for an effective treatment for coronavirus.
More than 50,000 Americans have died of coronavirus, and 890,000 have been infected.
Officials and doctors alike have hoped that hydroxychloroquine, a drug developed nearly half a century ago to treat malaria, might improve coronavirus patients’ odds by combating severe inflammation resulting from the viral infection.
In lab tests, the drug showed promise, appearing to quell the ‘cytokine storm’ of immune signalling cells that causes inflammation to run wild in the body, overwhelming the lungs.
Hydroxychloroquine interacts with the human immune response, making it useful in treating autoimmune diseases like lupus.
New York Governor Andrew Cuomo said on CNN last week that the review had shown no positive or negative effect
It was even added the official lists of treatments to try for doctors treating COVID-19 patients in China and South Korea, a French study suggested a near 100 percent recovery rate for those treated with hydroxychloroquine, and it was voted the most ‘effective’ treatment (anecdotally) in an international survey of doctors.
But the latest early results suggest that there’s no objective benefit from using the drug.
Of the 600-some coronavirus patients treated at 22 New York City area hospitals, some were treated with hydroxychloroquine alone, others were treated with the malaria drug plus the antibiotic azithromycin, and a third group got only the typical supportive care.
‘We don’t see a statistically significant difference between patients who took the drugs and those who did not,’ Dr David Holtgrave, who led the SUNY Albany study told CNN.
Notably, there were not higher rates of heart problems among the patients given hydroxychloroquine, despite the potential for dangerous arrhythmias as a side effect.
It comes after a Veteran Affairs study found that more COVID-19 patients treated with hydroxychloroquine died than did those who didn’t receive the drug.
Dr Holtgrave stressed, however, that the results of his stud are preliminary findings of an ongoing study that have not been peer-reviewed or published.
Dr Holtgrave and his team expect the full research, inclusive of 1,200 patients, will be ready for release as early as next week.
‘Hopefully what we’ve done here is to start collecting data and evidence and learning lessons as we go forward about effects and side effects,’ he told CNN.
Echoing Dr Holtgrave’s sentiments during CNN’s round table, Food and Drug Administration (FDA) Commissioner Dr Stephen Hahn said: ‘Obviously you need to wait for the entire cohort of individuals to have been treated with the complete course of treatment to get a full read on that.’
So far, the researchers have only revealed a hint at comparative survival rates, but the full study will also detail differing hospital stay lengths and whether patients treated or not treated with hydroxychloroquine had to be put in ICUs on ventilators, according to CNN.
By Mary Kekatos for DailyMail.com
The US Food and Drug Administration (FDA) has warned against using the anti-malaria drug hydroxychloroquine on coronavirus patients outside of hospital settings or clinical trials.
President Donald Trump has hailed the drug, which also is used to treat arthritis and lupus, as a ‘game-changer’ for treating COVID-19, the disease caused by the virus.
The federal health agency said it was issuing the warning after several reports of abnormal heart rhythms and rapid heart rates in patients who took the medication.
‘The FDA is aware of reports of serious heart rhythm problems in patients with COVID-19 treated with hydroxychloroquine or chloroquine, often in combination with azithromycin,’ the FDA wrote in a statement issued on Friday.
‘We are also aware of increased use of these medicines through outpatient prescriptions. Therefore, we would like to remind health care professionals and patients of the known risks associated with both hydroxychloroquine and chloroquine.’
The FDA issued a statement warning doctors against using hydroxychloroquine (pictured) on coronavirus patients outside of hospital settings or clinical trials
The agency said hydroxychloroquine can still be used in clinical trials or in some hospitalized patients.
It’s not immediately clear if any trials are in progress or planned trials will be halted based on the new guidance.
President Trump was among the first to wax lyrical about the possible benefits of hydroxychloroquine for coronavirus patients last month.
‘This would be a gift from heaven, this would be a gift from God if it works,’ he said during a press conference. ‘We are going to pray to God that it does work.’
He then repeated the claims on Twitter.
‘HYDROXYCHLOROQUINE & AZITHROMYCIN, taken together, have a real chance to be one of the biggest game changers in the history of medicine. The FDA has moved mountains – Thank You! Hopefully they will BOTH (H works better with A, International Journal of Antimicrobial Agents),’ he wrote in March.
President Donald Trump has touted the drug in as a potential ‘game-changer’ for treating coronavirus. Pictured: Trump during the White House coronavirus daily briefing, April 23
The study Trump refers to comes from Marseille, France, in which 30 patients were treated with hydroxychloroquine for 10 days combined with azithromycin, an antibiotic.
Although very small, the study ‘showed a significant reduction of the viral carriage’ after the six days and ‘much lower average carrying duration’ compared to patients who received other treatments.
One week later, the FDA issued an emergency use authorization for the drug, saying it could be used in hospitalized coronavirus patients with severe disease.
Several weeks later, the French study’s publisher said the paper ‘did not meet its standards’ because it excluded data on patients who did not respond well to the treatment.
Since then, much of the initial excitement surround hydroxychloroquine has died down.
In one study from the National Institutes of Health, 28 percent of US veterans with coronavirus who were treated with hydroxychloroquine died of the infection.
About 22 percent of those getting the anti-malaria drug plus antibiotic azithromycin died as well.
The FDA made its warning after several reports of abnormal heart rhythms and rapid heart rates in patients who took the medication. Pictured: Medics prepared to intubate a patient with COVID-19 symptoms at home
Additionally, the family of a New York woman with symptoms of COVID-19 told NBC News she died after her doctor prescribed her a combination of hydroxychloroquine and azithromycin.
The family says the physician did not confirm she had the virus nor test for heart problems before prescribing the drug.
And, earlier this month, the Centers for Disease Control and Prevention (CDC) removed highly unusual guidance from its website informing doctors on how to prescribe hydroxychlorquine.
Initially, the CDC webpage had read: ‘Although optimal dosing and duration of hydroxychloroquine for treatment of COVID-19 are unknown, some US clinicians have reported anecdotally.’
Now the website no longer includes that information. Instead, its first sentence says: ‘There are no drugs or other therapeutics approved by the US Food and Drug Administration to prevent or treat COVID-19.’
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