Hydroxychloroquine and azithromycin, which have been proposed for treatment of COVID-19 patients, are a potentially lethal combination and may have a serious impact on the cardiovascular system, according to a study.
The researchers, including those from Vanderbilt University and Stanford University in the US, carried out an observational, retrospective meta-analysis of a WHO database encompassing over 21 million adverse event case reports.
The reports span across all medication classes from over 130 countries between November 14, 1967, and March 1, 2020 — mainly before the COVID-19 pandemic.
The study, published in the journal Circulation, compared cardiovascular adverse-drug-reactions (CV-ADRs) in patients who received hydroxychloroquine, azithromycin, or the combination of both medications with all other cardiovascular medications in the database.
Hydroxychloroquine and azithromycin, alone or in combination, have been proposed for treatment of COVID-19 patients, the researchers said.
They explained that reports of potentially lethal acute cardiac proarrhythmogenic effects — promoting irregular heart rhythms — have been described mainly with azithromycin but also with hydroxychloroquine.
Their combination yielded an even stronger signal, the scientists said.
Hydroxychloroquine was also associated with potentially lethal heart failure when exposure was prolonged over several months, according to the researchers.
From the more than 21 million case reports of adverse drug reactions, the researchers extracted case reports for hydroxychloroquine and azithromycin, alone or in combination.
They found that 76,822 adverse event reports were associated with hydroxychloroquine alone, and in 28.4 percent of those cases (21,808), the drug was suspected to be associated with the adverse event.
The study found that 89,692 adverse event reports were associated with azithromycin alone, and in 60.8 per cent of those cases (54,533), the medication was suspected to be associated with the adverse events.
The researchers said 607 adverse event reports were associated with the combination of both medications.
Hydroxychloroquine was significantly associated with the development of conduction disorders, and heart failure, they said.
On Monday, the World Health Organization also suspended testing hydroxychloroquine in COVID-19 patients due to safety concerns, WHO Director-General Tedros Adhanom Ghebreyesus said.