A controversial drug taken by Donald Trump to ward off the coronavirus may be safer than sceptics initially thought, research suggests.
The president announced in May he had been taking the anti-malarial medication hydroxychloroquine for a week and a half, causing first-time prescription rates and online searches for the therapy to soar.
Hydroxychloroquine is not approved for the prevention or treatment of COVID-19, the disease caused by the coronavirus, in the UK or US.
The World Health Organization (WHO) stopped testing the drug after a Harvard study found patients on hydroxychloroquine were more likely to develop de-novo ventricular arrhythmia, the sudden onset of abnormal beating in the lower chambers of the heart.
This can cause the heart to beat too fast, preventing oxygen-rich blood from reaching the brain or triggering a cardiac arrest.
A team of European scientists has since found, however, hydroxychloroquine was not associated with deadly heart rhythms among patients with a low risk for arrhythmias.
The scientists stressed they only looked into hydroxychloroquine’s safety. When it comes to efficacy, evidence suggests the drug is ineffective in advanced COVID cases, however, the jury is out on whether it has benefits during the initial stages of ill health.
In June, editors of the prestigious medical journal The Lancet published an “Expression of Concern to alert readers to the fact that serious scientific questions have been brought to our attention”, citing the Harvard research.
The Harvard scientists found that out of more than 96,000 coronavirus patients, those given hydroxychloroquine were a third (33%) more likely to die than those receiving other forms of care.
This rose to a 44% higher risk when hydroxychloroquine was combined with an antibiotic from the class macrolides.
Those on hydroxychloroquine with a macrolide were also over five times more likely to develop a de-novo ventricular arrhythmia than those in the control group.
The research was said to have a “profound impact” on the WHO’s decision to stop testing the drug. This was met with criticism, with some experts questioning the robustness of the Harvard results.
“This is completely unjustified,” Professor Peter Horby from the University of Oxford said at the time.
“Even if the [Harvard] results were correct, observational data such as this, with its inherent weaknesses, should not be used to stop trials which will provide definitive and actionable answers.”
With safety and efficacy questions still lingering, a team of European scientists looked at 649 coronavirus patients between 10 March and 10 April.
The patients were first assessed for their QT prolongation risk, a sign of arrhythmias.
Hydroxychloroquine can cause a dangerous electrical change in the heart of some patients. This is called QT prolongation due to the pattern it makes on an electrocardiogram.
Although the drug has been used for decades for other conditions, the coronavirus pandemic is the first time it has been taken by large numbers of acutely ill patients with multiple health conditions, who may also be on other drugs that cause QT prolongation as a side effect.
The scale of the coronavirus outbreak raises the risk any one patient may have a pre-existing heart condition that predisposes them to arrhythmias.
Changes in blood electrolytes – electrically-charged minerals in the body that can trigger arrhythmias – can also occur in those needing intensive care.
Once the participants’ QT prolongation risk was found to be low, they were given 200mg of hydroxychloroquine twice a day.
More than half (58.6%) took a “loading dose” – an initial large dose of a medicine to ensure a quick therapeutic response – on the first day.
Hydroxychloroquine was administered soon after symptom onset in three settings: 126 (19.4%) patients were managed at home, 495 (76.3%) were in a hospital ward and 28 (4.3%) were in intensive care.
To mirror real-world conditions, around a third (30%) of the patients were on two drugs that can cause QT prolongation – one being hydroxychloroquine, and 13.6% were taking three of the medications.
The results – published in the journal EP Europace – revealed a statistically significant increase in QT prolongation across all three settings, however, this was modest and similar regardless of where the patient was treated.
Around 16 days after taking hydroxychloroquine, none of the arrhythmias that occurred were lethal.
Seven (1.1%) of the participants had a serious ventricular arrhythmia, which the scientists did not link to hydroxychloroquine.
“Hydroxychloroquine treatment was associated with QT prolongation, as expected, but the change was small,” said study author Dr Alessio Gasperetti from the Monzino Cardiology Centre in Milan.
“There was no connection between the drug and the occurrence of arrhythmias.
“The study shows hydroxychloroquine administration, alone or in combination with other potentially QT-prolonging drugs, is safe for short-term treatment of COVID-19 patients at home or in hospital, provided they undergo risk assessment and ECG [electrocardiogram] monitoring by a physician.”
When it comes to the drug’s efficacy, Dr Anthony Fauci – director of the US National Institute of Allergy and Infectious Diseases – told the BBC in July “every single good study has shown hydroxychloroquine is not effective in the treatment of COVID-19”.
The US Food and Drug Administration “cautions against use of hydroxychloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems”.
The US Centers for Disease Control and Prevention has also said “current data indicate the potential benefits of these drugs do not outweigh their risks”.
Other experts have called for further research.
“This is a drug that is very widely used for a disease that kills hundreds of thousands of people, but on the basis of no good evidence,” Professor Martin Landray from the University of Oxford previously said.
“The sooner we get answers from randomised controlled trials the better.
“If it turns out hydroxychloroquine is effective for COVID-19, then let’s use it; if not, let’s abandon it. But this is not a time for speculation.”