The therapeutic combination hydroxychloroquine (or chloroquine) and new generation macrolide is rather associated with an increase in mortality and the risk of ventricular arrhythmias in Covid-19 patients diagnosed and hospitalized for less than 48 hours. Following the publication of these new elements, the Minister of Health decided to review the rules for prescribing these drugs.
- A comparison of nearly 15,000 patients does not demonstrate the benefit of chloroquine in the treatment of Covid-19
- This treatment would be associated with a higher risk of mortality
In the absence of the results of the first randomized hydroxychloroquine-macrolide studies, a new international registry has been organized to get an idea of the interest of this combination on a very large population of Covid-19 patients. The study is published in the Lancet.
Following this publication, the Minister of Health, Olivier Véran, announced his intention to review the rules for prescribing these treatments.
This comparison of nearly 15,000 patients treated less than 48 hours after diagnosis versus 81,000 controls finds no argument in favor of the effectiveness of the combination of hydroxychloroquine (or chloroquine) and new generation macrolide. On the other hand, this type of combined therapeutic strategy is associated with excess mortality and seems to cause a significant number of ventricular arrhythmias.
Excess mortality of the treatment groups
The four treatment groups were all associated with a significantly higher risk of mortality than in the control group (which was 9.3%): 18% of deaths for hydroxychloroquine alone, 23.8% when it was associated with a macrolide, 16.4% for chloroquine alone, 22.2% when it was combined with the antibiotic (significant differences).
The authors thus estimate that the risk of mortality would be 30 to 45% higher in patients taking these treatments compared to the control group of patients hospitalized for hypoxemic pneumonia.
Increased risk of ventricular arrhythmia
Regarding the risk of serious ventricular arrhythmias, and compared to the control group (0.3%), it is significantly more frequent in patients who receive hydroxychloroquine (6.1%), the hydroxychloroquine-macrolide combination ( 8%), chloroquine (4.3%) and the chloroquine-macrolide combination (6.5%).
The risk of arrhythmia would be five times higher with the association of these two types of molecules according to the authors, even if the causal link cannot be directly demonstrated.
An international registry of nearly 100,000 hospitalized patients
The registry collected data from approximately 96,032 patients infected with the SARS-CoV-2 virus (53.8 years of average age), admitted and treated within 48 hours of diagnosis, in 671 hospitals around the world ( including 46.3% women).
About 15,000 of them (n=14,888) received one of the four combinations studied: chloroquine alone (n=1868) or associated with a new generation macrolide (n=3783; azithromycin or clarithromycin), hydroxychloroquine alone (n=3016) or combined with this same type of antibiotic (n=6221).
Hospitalized patients treated in less than 48 hours
These four groups were compared to the 81,000 patients in the control group who had not received this treatment. Adjustments were made for age, gender, BMI, smoking status, comorbidities and disease severity scores.
Patients for whom one of the treatments tested was initiated more than 48 hours after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The primary endpoints are in-hospital mortality and occurrence of ventricular arrhythmias (ventricular tachycardia or ventricular fibrillation).
Excess mortality to be confirmed
The authors are asking for “urgent” confirmation via randomized clinical trials before any firm conclusions are reached, so that’s not the end of the story yet. Only randomized studies, and in particular those carried out in patients in town, less severe, will make it possible to answer all the objections of aficionados of the Marseille protocol.
This therapeutic strategy was based on very little (no studies of value) and triggered an avalanche of therapeutic trials (more than 100 worldwide) which hampered the recruitment of patients in studies on the relevant strategies. We have been given hydroxychloroquine every epidemic or pandemic for almost 60 years with the same results…
An option endorsed by the Minister of Health, Olivier Véran, who asked the High Council for Public Health (HCSP), on Saturday May 23, to propose “within 48 hours a revision of the derogatory rules of prescription” of various treatments, including hydroxychloroquine, according to France Info.
In the absence of the results of the first randomized hydroxychloroquine-macrolide studies, a new international registry has been organized to get an idea of the interest of this combination on a very large population of Covid-19 patients. The study is published in the Lancet.
Following this publication, the Minister of Health, Olivier Véran, announced his intention to review the rules for prescribing these treatments.
This comparison of nearly 15,000 patients treated less than 48 hours after diagnosis versus 81,000 controls finds no argument in favor of the effectiveness of the combination of hydroxychloroquine (or chloroquine) and new generation macrolide. On the other hand, this type of combined therapeutic strategy is associated with excess mortality and seems to cause a significant number of ventricular arrhythmias.
Excess mortality of the treatment groups
The four treatment groups were all associated with a significantly higher risk of mortality than in the control group (which was 9.3%): 18% of deaths for hydroxychloroquine alone, 23.8% when it was associated with a macrolide, 16.4% for chloroquine alone, 22.2% when it was combined with the antibiotic (significant differences).
The authors thus estimate that the risk of mortality would be 30 to 45% higher in patients taking these treatments compared to the control group of patients hospitalized for hypoxemic pneumonia.
Increased risk of ventricular arrhythmia
Regarding the risk of serious ventricular arrhythmias, and compared to the control group (0.3%), it is significantly more frequent in patients who receive hydroxychloroquine (6.1%), the hydroxychloroquine-macrolide combination ( 8%), chloroquine (4.3%) and the chloroquine-macrolide combination (6.5%).
The risk of arrhythmia would be five times higher with the association of these two types of molecules according to the authors, even if the causal link cannot be directly demonstrated.
An international registry of nearly 100,000 hospitalized patients
The registry collected data from approximately 96,032 patients infected with the SARS-CoV-2 virus (53.8 years of average age), admitted and treated within 48 hours of diagnosis, in 671 hospitals around the world ( including 46.3% women).
About 15,000 of them (n=14,888) received one of the four combinations studied: chloroquine alone (n=1868) or associated with a new generation macrolide (n=3783; azithromycin or clarithromycin), hydroxychloroquine alone (n=3016) or combined with this same type of antibiotic (n=6221).
Hospitalized patients treated in less than 48 hours
These four groups were compared to the 81,000 patients in the control group who had not received this treatment. Adjustments were made for age, gender, BMI, smoking status, comorbidities and disease severity scores.
Patients for whom one of the treatments tested was initiated more than 48 hours after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The primary endpoints are in-hospital mortality and occurrence of ventricular arrhythmias (ventricular tachycardia or ventricular fibrillation).
Excess mortality to be confirmed
The authors are asking for “urgent” confirmation via randomized clinical trials before any firm conclusions are reached, so that’s not the end of the story yet. Only randomized studies, and in particular those carried out in patients in town, less severe, will make it possible to answer all the objections of aficionados of the Marseille protocol.
This therapeutic strategy was based on very little (no studies of value) and triggered an avalanche of therapeutic trials (more than 100 worldwide) which hampered the recruitment of patients in studies on the relevant strategies. We have been given hydroxychloroquine every epidemic or pandemic for almost 60 years with the same results…
An option endorsed by the Minister of Health, Olivier Véran, who asked the High Council for Public Health (HCSP), on Saturday May 23, to propose “within 48 hours a revision of the derogatory rules of prescription” of various treatments, including hydroxychloroquine, according to France Info.
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