Cardiovascular Safety of COVID-19 Treatments: A Disproportionality Analysis of Adverse Event Reports from the WHO VigiBase.

IF 5.3 3区医学 Q1 INFECTIOUS DISEASES

Infectious Diseases and Therapy Pub Date : 2025-10-01 Epub Date: 2025-09-11 DOI:10.1007/s40121-025-01225-z

Hoi K Cheng, Angel Lai, Maxwell Kwok, Bryan P Yan, Ellen Ngar-Yun Poon

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引用次数: 0

Abstract

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.

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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

2019冠状病毒病（COVID-19）的高死亡率凸显了安全有效的抗病毒治疗的必要性。小分子抗病毒药物（remdesivir, molnupiravir, nirmatrelvir/ritonavir）和免疫调节剂（baricitinib, tocilizumab）已被开发或重新用于抑制病毒复制和改善细胞因子风暴。尽管美国食品和药物管理局（FDA）批准，严重的心血管不良事件（CVAEs）可能在初始试验中不明显。方法：使用世界卫生组织（WHO） VigiBase数据库，对2020年3月至2023年7月期间与世界卫生组织（WHO）推荐的五种COVID-19治疗方法相关的CVAEs进行回顾性分析。计算具有95%置信区间（CI）的调整报告优势比（aROR）来评估CVAE风险。结果：共报告276631例ae与COVID-19相关，其中13091例归类为心血管事件。Remdesivir与CVAEs的发生率显著增加相关，尤其是心动过缓（aROR 2.4, 95% CI 2.28-2.52）。相反，nirmatrelvir/ritonavir和molnupiravir的CVAEs发生率降低。在免疫调节剂中，baricitinib与CVAEs风险增加相关（aROR为2.31,95% CI为2.09 -2.59），其中深静脉血栓形成最为突出（aROR为45.34,95% CI为34.89-58.9），占数据库中报告研究病例的38.8%。此外，与前欧米克隆时期相比，欧米克隆时期的CVAEs几率更高。结论：这些发现强调了持续药物警戒的重要性，并提示COVID-19免疫调节剂之间潜在的CV安全性差异。由于托珠单抗和巴西替尼同样适用于COVID-19重症患者，因此需要进一步的临床试验来探索托珠单抗是否代表这些患者比巴西替尼更安全的替代方案。这项研究的见解可能指导未来抗病毒药物的再利用和大流行防备策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Infectious Diseases and Therapy Medicine-Microbiology (medical)

CiteScore

8.60

自引率

1.90%

发文量

136

审稿时长

6 weeks

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.