Risk of drug-induced Long QT Syndrome associated with the use of repurposed COVID-19 drugs: a systematic review
Risk of drug-induced Long QT Syndrome associated with the use of repurposed COVID-19 drugs: a systematic review
Objective: To determine the relative risk of drug-induced Long QT Syndrome (LQTS) associated with SARS-CoV-2 (COVID-19) proposed repurposed drugs compared to well-known torsadogenic compounds. Setting: Computer calculations and simulations were performed using primary pharmacokinetic and pharmacodynamic data for each proposed drug. Seven different LQTS indices were calculated and compared. The U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried with specific key words relating to arrhythmogenic events. Interventions: A thorough literature search was performed to gather information on the pharmacological properties of six drugs (azithromycin, chloroquine, favipiravir, hydroxychloroquine, lopinavir/ritonavir, and remdesivir) repurposed to treat COVID-19. Researchers emphasized the affinity of these drugs to block the rapid component of the delayed rectifier cardiac potassium current (IKr) encoded by the human ether-a-go-go gene (hERG), their propensity to prolong cardiac repolarization (QT interval), and cause torsade de pointes (TdP). The risk of drug-induced LQTS for these drugs was quantified by comparing six indices that assess such risk. Primary and secondary outcome measures: Level of risk estimated for the six COVID-19 drugs being proposed compared to 23 torsadogenic drugs. Number of proarrhythmic adverse events identified for these drugs in the FAERS. Results: Estimators of LQTS risk levels indicated a very high or high risk for all COVID-19 repurposed drugs with the exception for azithromycin, although cases of TdP have been reported with this drug. There was excellent agreement among the various indices used to assess risk of drug-induced LQTS for the six repurposed drugs and 23 torsadogenic compounds. Conclusion: The risk-benefit assessment for the use of repurposed drugs to treat COVID-19 is complicated since benefits are currently anticipated, not proven. Mandatory monitoring of the QT interval shall be performed, as such monitoring is possible for hospitalized patients or with the use of biodevices for outpatients prescribed these drugs.
- University of Montreal Canada
- University of Florida United States
- Instituto United States
- Florida Southern College United States
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citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).0 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Average citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).0 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Average
Citations provided by BIP!Popularity provided by BIP!- University of Montreal Canada
- University of Florida United States
- Instituto United States
- Florida Southern College United States
Objective: To determine the relative risk of drug-induced Long QT Syndrome (LQTS) associated with SARS-CoV-2 (COVID-19) proposed repurposed drugs compared to well-known torsadogenic compounds. Setting: Computer calculations and simulations were performed using primary pharmacokinetic and pharmacodynamic data for each proposed drug. Seven different LQTS indices were calculated and compared. The U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried with specific key words relating to arrhythmogenic events. Interventions: A thorough literature search was performed to gather information on the pharmacological properties of six drugs (azithromycin, chloroquine, favipiravir, hydroxychloroquine, lopinavir/ritonavir, and remdesivir) repurposed to treat COVID-19. Researchers emphasized the affinity of these drugs to block the rapid component of the delayed rectifier cardiac potassium current (IKr) encoded by the human ether-a-go-go gene (hERG), their propensity to prolong cardiac repolarization (QT interval), and cause torsade de pointes (TdP). The risk of drug-induced LQTS for these drugs was quantified by comparing six indices that assess such risk. Primary and secondary outcome measures: Level of risk estimated for the six COVID-19 drugs being proposed compared to 23 torsadogenic drugs. Number of proarrhythmic adverse events identified for these drugs in the FAERS. Results: Estimators of LQTS risk levels indicated a very high or high risk for all COVID-19 repurposed drugs with the exception for azithromycin, although cases of TdP have been reported with this drug. There was excellent agreement among the various indices used to assess risk of drug-induced LQTS for the six repurposed drugs and 23 torsadogenic compounds. Conclusion: The risk-benefit assessment for the use of repurposed drugs to treat COVID-19 is complicated since benefits are currently anticipated, not proven. Mandatory monitoring of the QT interval shall be performed, as such monitoring is possible for hospitalized patients or with the use of biodevices for outpatients prescribed these drugs.