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Risk versus Benefit of Using Hydroxychloroquine to Treat Patients with COVID-19
George G Zhanel1, Michael A Zhanel1, Kevin F Boreskie1
1Department of Medical Microbiology/Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Insights
Hydroxychloroquine (HCQ) showed early promise for COVID-19 treatment but extensive research found no benefit. Serious adverse events associated with HCQ use outweigh any potential advantages, recommending against its use for COVID-19.
Area of Science:
- Pharmacology
- Infectious Diseases
- Clinical Medicine
Background:
- Hydroxychloroquine (HCQ) has a long history treating malaria, lupus, and rheumatoid arthritis.
- HCQ and chloroquine (CQ) initially showed in vitro antiviral activity against SARS-CoV-2.
- Early studies suggested potential benefits of HCQ/CQ for COVID-19 patients.
Purpose of the Study:
- To review adverse events of HCQ used alone or with azithromycin (AZ) in COVID-19 patients.
- To assess the risk-benefit profile of HCQ for COVID-19 treatment and prevention.
- To provide evidence-based recommendations on HCQ use for COVID-19.
Main Methods:
- Systematic review of randomized controlled trials, meta-analyses, and clinical data.
- Analysis of reported adverse events associated with HCQ and HCQ/AZ treatment.
- Comparison of clinical outcomes and adverse event profiles.
Main Results:
- Numerous studies demonstrate no mortality or recovery benefit for HCQ in hospitalized COVID-19 patients.
- HCQ use, alone or with AZ, is linked to cardiac, neuropsychiatric, hematologic, and hepatobiliary adverse events.
- The risks of adverse events significantly outweigh potential benefits.
Conclusions:
- HCQ use (with or without AZ) in COVID-19 patients is associated with considerable risks.
- The available evidence strongly supports against the use of HCQ for COVID-19 treatment or prevention.
- Clinical decision-making should prioritize patient safety and evidence-based therapies.
Abstract:
Hydroxychloroquine (HCQ), also known by its trade name Plaquenil®, has been used for over 50 years as a treatment for malaria, systemic lupus erythematosus, and rheumatoid arthritis. As the COVID-19 pandemic emerged in the United States and globally in early 2020, HCQ began to garner attention as a potential treatment and as prophylaxis against COVID-19. Preliminary data indicated that HCQ as well as chloroquine (CQ) possessed in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early clinical data from China and France reported that HCQ and CQ were associated with viral load reduction and clinical improvement in patients with COVID-19 compared to control groups; however, an overwhelming number of randomized controlled trials, meta-analyses, and systematic reviews have since concluded that HCQ used alone, or in combination with azithromycin (AZ), provides no mortality or time-to-recovery benefit in hospitalized patients with COVID-19. Additionally, these same trials reported adverse events including cardiac, neuropsychiatric, hematologic, and hepatobiliary manifestations in patients with COVID-19 whom had been treated with HCQ. This review article summarizes the available data pertaining to the adverse events associated with HCQ use, alone or in combination with azithromycin, in patients with COVID-19 in order to fully assess the risk versus benefit of treating COVID-19 patients with these agents. The results of this review lead us to conclude that the risks of adverse events associated with HCQ use (with or without AZ) outweigh the potential clinical benefits and thus recommend against its use in the treatment or prevention of COVID-19.
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