According to a paper published in the medical journal Lancet which analysed data of over 96,000 Covid-19 patients sourced from 671 hospitals across six continents over a span of almost four months, the benefits of administering hydroxychloroquine or chloroquine when used alone or in combination with a macrolide, to a Covid-19 positive patient are unconfirmed. In fact, the findings demonstrate that these drug regimens were associated with higher mortality rate or decreased in-hospital survival and an increased frequency of irregular heart rhythm or arrhythmia (ventricular arrhythmias) when used for treatment of Covid-19.
The findings come from one of the largest analyses of the risks and benefits associated with treating coronavirus patients with the above mentioned anti-malarial drugs. It is based on a retrospective analysis of medical records and is not a controlled study.
The paper co-authored by Mandeep R Mehra, Sapan S Desai, Frank Ruschitzka and Amit N Patel points out that chloroquine is an antimalarial drug while hydroxychloroquine, is used for the treatment of autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. These drugs have shown to have antiviral properties as well as immunomodulatory effects in laboratory conditions and were thus being repurposed as therapeutic agents in the absence of an effective treatment against severe acute respiratory syndrome coronavirus 2, better known as SARS-CoV-2 infection.
“However, the use of this class of drugs for COVID-19 is based on a small number of anecdotal experiences that have shown variable responses in uncontrolled observational analyses, and small, open-label, randomised trials, that have largely been inconclusive,” says the paper.
It says that one of the several protocols developed for Covid-19 treatment, also advocates the use of a combination of hydroxychloroquine with a second-generation macrolide, such as azithromycin (or clarithromycin).
The paper, however, deduces from “in-hospital outcomes” that these drugs either administered alone or in combination with macrolides have shown a higher mortality rate and increased heart problems for the researched group.
The research paper assumes significance since antimalarial drugs are being experimented with for the treatment of coronavirus cases in several countries including the United States, which has shown even greater reliance on these drugs to treat positive cases. In India, ICMR has not allowed use of these drugs for coronavirus treatment on a ‘sympathetic’ basis. While US President Donald Trump had personally intervened and requested India for lifting the ban on export of hydroxychloroquine, India has warned against the indiscriminate use of this medicine among Covid-19 patients and suspects.
The multinational registry analysis comprised data of patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. It included patients in four treatment groups—chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide. All these patients had received one of the four treatments within 48 hours of diagnosis of the disease.
Another group—a control group—comprised of hospitalized coronavirus patients who had not been given any of the four treatments under study, was formed.
The research studied the in-hospital mortality and the occurrence of de-novo ventricular arrhythmias among the groups formed.
The 96 032 studied patients had a mean age of 53·8 years and 46·3% of those were women. Of these, 14 888 patients were in the treatment groups—1,868 received chloroquine, 3,783 received chloroquine with a macrolide, 3,016 received hydroxychloroquine, and 6,221 received hydroxychloroquine with a macrolide
and 81, 144 patients were in the control group.
The study found that 10, 698 or 11·1% patients died in the hospital. The mortality in the control group was 9·3%, but for the group administered with hydroxychloroquine, it was 18·0% (hazard ratio 1·335, 95% CI 1·223–1·457), for the group given hydroxychloroquine with a macrolide, it was 23·8% (hazard ratio 1·447, 1·368–1·531), for the group given chloroquine, it was 16·4% (hazard ratio 1·365, 1·218–1·531), and for group that was administered chloroquine with a macrolide, it was 22·2% (hazard ratio 1·368, 1·273–1·469).
Each of these four groups were independently associated with an increased risk of in-hospital mortality, found the study.
The occurrence of de-novo ventricular arrhythmia was also higher among the four groups administered with the drugs of interest, compared to the control group.
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“Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935–2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106–5·983), chloroquine (4·3%; 3·561, 2·760–4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344–4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalization,” the study said.
The study claims that the analysis was arrived at after controlling for multiple confounding factors including age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity.
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