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Deaths induced by compassionate use of hydroxychloroquine during the first COVID-19 wave: an estimate

Pradelle et al., Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2023.116055
Jan 2024  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020, now with p < 0.00000000001 from 419 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19hcq.org
This study was retracted due to unreliable data and invalid assumptions.
Highly flawed analysis using an incorrect estimate of mortality from Axfors et al.
Axfors et al. assign 89% weight to the RECOVERY and SOLIDARITY trials, producing the same result. These trials used excessively high non-patient-customized dosage in very sick late stage patients, results are not generalizable to typical dosage or earlier treatment. For CQ, 97% weight is assigned to Borba et al., a study that does not have a control group (the study compares two different dosages of CQ).
For more discussion of flaws see twitter.com and pubpeer.com.
Beaudart et al.4 confirm that, among very late treatment studies, excess mortality is only seen with excessive dosage.
Using the 7 million estimated COVID-19 deaths from OWID5 we can estimate the number of lives that could have been saved by HCQ use:
1.6 million fewer deaths, based on 213 late treatment mortality results6.
5.3 million fewer deaths, based on 14 early treatment mortality results6.
This does not account for patients saved by the limited use before or against the politicization, patients that died due to excessive dosage/very late treatment, or the use of other effective treatments.
9 meta analyses show significant improvements with hydroxychloroquine for mortality7-10, hospitalization7, recovery11, combined death/hospitalization/cases12, cases13,14, and viral clearance15.
Currently there are 38 HCQ for COVID-19 early treatment studies, showing 76% lower mortality [61‑85%], 67% lower ventilation [-710‑99%], 31% lower ICU admission [1‑53%], and 41% lower hospitalization [28‑51%].
Pradelle et al., 2 Jan 2024, peer-reviewed, 6 authors. Contact: jean-christophe.lega@chu-lyon.fr.
This PaperHCQAll
Deaths induced by compassionate use of hydroxychloroquine during the first COVID-19 wave: an estimate
Alexiane Pradelle, Sabine Mainbourg, Steeve Provencher, Emmanuel Massy, Guillaume Grenet, Jean-Christophe Lega
Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2023.116055
Background: During the first wave of COVID-19, hydroxychloroquine (HCQ) was used off-label despite the absence of evidence documenting its clinical benefits. Since then, a meta-analysis of randomised trials showed that HCQ use was associated with an 11% increase in the mortality rate. We aimed to estimate the number of HCQ-related deaths worldwide. Methods and findings: We estimated the worldwide in-hospital mortality attributable to HCQ use by combining the mortality rate, HCQ exposure, number of hospitalised patients, and the increased relative risk of death with HCQ. The mortality rate in hospitalised patients for each country was calculated using pooled prevalence estimated by a meta-analysis of published cohorts. The HCQ exposure was estimated using median and extreme estimates from the same systematic review. The number of hospitalised patients during the first wave was extracted from dedicated databases. The systematic review included 44 cohort studies (Belgium: k = 1, France: k = 2, Italy: k = 12, Spain: k = 6, Turkey: k = 3, USA: k = 20). HCQ prescription rates varied greatly from one country to another (range 16-84%). Overall, using median estimates of HCQ use in each country, we estimated that 16,990 HCQ-related in-hospital deaths (range 6267-19256) occurred in the countries with available data. The median number of HCQ-related deaths in Belgium, Turkey, France, Italy, Spain, and the USA was 240 (range not estimable), 95 (range 92-128), 199 (range not estimable), 1822 (range 1170-2063), 1895 (range 1475-2094) and 12739 (3244-15570), respectively. Conclusions: Although our estimates are limited by their imprecision, these findings illustrate the hazard of drug repurposing with low-level evidence.
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