Hoi K Cheng, Angel Lai, Maxwell Kwok, Bryan P Yan, Ellen Ngar-Yun Poon
{"title":"COVID-19治疗的心血管安全性：来自WHO viibase的不良事件报告的歧化分析","authors":"Hoi K Cheng, Angel Lai, Maxwell Kwok, Bryan P Yan, Ellen Ngar-Yun Poon","doi":"10.1007/s40121-025-01225-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The high mortality of Coronavirus Disease 2019 (COVID-19) highlights the need for safe and effective antiviral treatment. Small molecular antivirals (remdesivir, molnupiravir, nirmatrelvir/ritonavir) and immunomodulators (baricitinib, tocilizumab) have been developed or repurposed to suppress viral replication and ameliorate cytokine storms, respectively. Despite U.S. Food and Drug Administration (FDA) approval, serious cardiovascular adverse events (CVAEs) may not be apparent in initial trials.</p><p><strong>Methods: </strong>A retrospective analysis of CVAEs linked to five World Health Organization (WHO) recommended COVID-19 therapies was conducted using the WHO VigiBase database from March 2020 to July 2023. Adjusted reporting odds ratios (aROR) with 95% confidence intervals (CI) were calculated to assess CVAE risks.</p><p><strong>Results: </strong>A total of 276,631 AEs were reported to be associated with COVID-19, of which 13,091 were classified as cardiovascular events. Remdesivir was associated with significantly increased odds of CVAEs, particularly bradycardia (aROR 2.4, 95% CI 2.28-2.52). In contrast, nirmatrelvir/ritonavir and molnupiravir showed reduced CVAEs odds. Among immunomodulators, baricitinib was associated with increased CVAEs risk (aROR 2.31, 95% CI 2.07-2.59), with deep vein thrombosis being the most prominent (aROR 45.34, 95% CI 34.89-58.9), accounting for 38.8% of reported study cases in the database. Also, CVAEs odds were higher during the Omicron period compared to pre-Omicron period.</p><p><strong>Conclusions: </strong>These findings highlight the importance of continued pharmacovigilance and suggest potential CV safety differences among COVID-19 immunomodulators. Since tocilizumab and baricitinib are similarly indicated for severe patients with COVID-19, further clinical trials are warranted to explore whether tocilizumab represents a safer alternative to baricitinib for these patients. Insights from this study may guide future antiviral repurposing and pandemic preparedness strategies.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":"2445-2463"},"PeriodicalIF":5.3000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480238/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cardiovascular Safety of COVID-19 Treatments: A Disproportionality Analysis of Adverse Event Reports from the WHO VigiBase.\",\"authors\":\"Hoi K Cheng, Angel Lai, Maxwell Kwok, Bryan P Yan, Ellen Ngar-Yun Poon\",\"doi\":\"10.1007/s40121-025-01225-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>The high mortality of Coronavirus Disease 2019 (COVID-19) highlights the need for safe and effective antiviral treatment. Small molecular antivirals (remdesivir, molnupiravir, nirmatrelvir/ritonavir) and immunomodulators (baricitinib, tocilizumab) have been developed or repurposed to suppress viral replication and ameliorate cytokine storms, respectively. Despite U.S. Food and Drug Administration (FDA) approval, serious cardiovascular adverse events (CVAEs) may not be apparent in initial trials.</p><p><strong>Methods: </strong>A retrospective analysis of CVAEs linked to five World Health Organization (WHO) recommended COVID-19 therapies was conducted using the WHO VigiBase database from March 2020 to July 2023. Adjusted reporting odds ratios (aROR) with 95% confidence intervals (CI) were calculated to assess CVAE risks.</p><p><strong>Results: </strong>A total of 276,631 AEs were reported to be associated with COVID-19, of which 13,091 were classified as cardiovascular events. Remdesivir was associated with significantly increased odds of CVAEs, particularly bradycardia (aROR 2.4, 95% CI 2.28-2.52). In contrast, nirmatrelvir/ritonavir and molnupiravir showed reduced CVAEs odds. Among immunomodulators, baricitinib was associated with increased CVAEs risk (aROR 2.31, 95% CI 2.07-2.59), with deep vein thrombosis being the most prominent (aROR 45.34, 95% CI 34.89-58.9), accounting for 38.8% of reported study cases in the database. Also, CVAEs odds were higher during the Omicron period compared to pre-Omicron period.</p><p><strong>Conclusions: </strong>These findings highlight the importance of continued pharmacovigilance and suggest potential CV safety differences among COVID-19 immunomodulators. Since tocilizumab and baricitinib are similarly indicated for severe patients with COVID-19, further clinical trials are warranted to explore whether tocilizumab represents a safer alternative to baricitinib for these patients. 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Cardiovascular Safety of COVID-19 Treatments: A Disproportionality Analysis of Adverse Event Reports from the WHO VigiBase.
Introduction: The high mortality of Coronavirus Disease 2019 (COVID-19) highlights the need for safe and effective antiviral treatment. Small molecular antivirals (remdesivir, molnupiravir, nirmatrelvir/ritonavir) and immunomodulators (baricitinib, tocilizumab) have been developed or repurposed to suppress viral replication and ameliorate cytokine storms, respectively. Despite U.S. Food and Drug Administration (FDA) approval, serious cardiovascular adverse events (CVAEs) may not be apparent in initial trials.
Methods: A retrospective analysis of CVAEs linked to five World Health Organization (WHO) recommended COVID-19 therapies was conducted using the WHO VigiBase database from March 2020 to July 2023. Adjusted reporting odds ratios (aROR) with 95% confidence intervals (CI) were calculated to assess CVAE risks.
Results: A total of 276,631 AEs were reported to be associated with COVID-19, of which 13,091 were classified as cardiovascular events. Remdesivir was associated with significantly increased odds of CVAEs, particularly bradycardia (aROR 2.4, 95% CI 2.28-2.52). In contrast, nirmatrelvir/ritonavir and molnupiravir showed reduced CVAEs odds. Among immunomodulators, baricitinib was associated with increased CVAEs risk (aROR 2.31, 95% CI 2.07-2.59), with deep vein thrombosis being the most prominent (aROR 45.34, 95% CI 34.89-58.9), accounting for 38.8% of reported study cases in the database. Also, CVAEs odds were higher during the Omicron period compared to pre-Omicron period.
Conclusions: These findings highlight the importance of continued pharmacovigilance and suggest potential CV safety differences among COVID-19 immunomodulators. Since tocilizumab and baricitinib are similarly indicated for severe patients with COVID-19, further clinical trials are warranted to explore whether tocilizumab represents a safer alternative to baricitinib for these patients. Insights from this study may guide future antiviral repurposing and pandemic preparedness strategies.
期刊介绍：
Infectious Diseases and Therapy is an international, open access, peer-reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of infectious disease therapies and interventions, including vaccines and devices. Studies relating to diagnostic products and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
Areas of focus include, but are not limited to, bacterial and fungal infections, viral infections (including HIV/AIDS and hepatitis), parasitological diseases, tuberculosis and other mycobacterial diseases, vaccinations and other interventions, and drug-resistance, chronic infections, epidemiology and tropical, emergent, pediatric, dermal and sexually-transmitted diseases.
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