“Deaths Induced by Compassionate Use of Hydroxychloroquine during the First COVID-19 Wave: an Estimate”, 2024-02 ():
Hydroxychloroquine (HCQ) was prescribed in hospitalized patients with Covid-19 despite of the low-level evidence.
Subsequently, HCQ use was associated with an 11% increase in the mortality rate in a meta-analysis of randomized trials.
The number of HCQ related deaths in hospitalized patients is estimated at 16,990 in 6 countries.
These findings illustrate the hazard of drug repurposing with low-level evidence for the management of future pandemics.
Background: During the first wave of COVID-19, HCQ was used off-label despite the absence of evidence documenting its clinical benefits. Since then, a meta-analysis of randomized 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.
Method: We estimated the worldwide in-hospital mortality attributable to HCQ use by combining the mortality rate, HCQ exposure, number of hospitalized patients, and the increased relative risk of death with HCQ. The mortality rate in hospitalized 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 hospitalized 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).
Findings: 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 6,267–19,256) 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), 1,822 (range 1,170–2,063), 1,895 (range 1,475–2,094) and 12,739 (3,244–15,570), respectively.
Conclusion: Although our estimates are limited by their imprecision, these findings illustrate the hazard of drug repurposing with low-level evidence.
[Keywords: Covid-19, off-label treatment, safety, repurposing]