Department of Pharmacy, University of Alabama at Birmingham Hospital, Birmingham, Alabama, USA.
Department of Research, Baptist Hospitals of Southeast Texas, Beaumont, Texas, USA.
Pharmacotherapy. 2024 Mar;44(3):214-223. doi: 10.1002/phar.2896. Epub 2023 Dec 8.
Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs) and anti-angiogenics, are first-line therapies for advanced and metastatic hepatocellular carcinoma. Although TKIs have a greater potential for off-target adverse effects compared with bevacizumab (anti-angiogenics), a direct comparison of the risk of cardiovascular adverse events between these two types of therapies has not been performed.
To compare the incidence of and characterize cardiovascular adverse events in patients with hepatocellular carcinoma receiving TKIs versus bevacizumab.
This cohort study included adult patients with hepatocellular carcinoma who received first-line TKIs (sorafenib or lenvatinib) or bevacizumab at two academic medical centers and one community cancer center from September 2018 to August 2021. The primary outcome was risk of cardiovascular adverse events. Major secondary outcomes included the incidence of individual types of cardiovascular adverse events and risk factors associated with major adverse cardiovascular events (MACE).
The study included 221 patients (159 TKI patients; 62 bevacizumab patients). At a median follow-up of 5 months, the probability of cardiovascular adverse events was not significantly different between the two groups (hazard ratio [HR]: 0.85; 95% confidence interval [95% CI]: 0.58-1.24; p = 0.390). The cumulative incidence of cardiovascular events was highest in patients receiving lenvatinib (sub-distribution hazard ratio [SHR]: 1.53; 95% CI: 1.02-2.30) compared with those receiving sorafenib (reference) or bevacizumab (SHR: 1.05; 95% CI: 0.68-1.64) after adjustment for comorbidities, liver transplant status, and presence of portal vein thrombosis at baseline. Cardiovascular adverse events were observed in 151 (68%) patients, and MACE were observed in 27 (12%) patients. Risk factors associated with MACE were hypertension (SHR: 3.5; 95% CI: 0.9087-15.83; p = 0.086), prior history of MACE (SHR: 2.01; 95% CI: 0.83-4.87; p = 0.124), and tobacco use (SHR: 2.85; 95% CI: 0.90-8.97; p = 0.074).
Cardiovascular risk was not significantly different between TKIs and bevacizumab. Lenvatinib appears to have the highest risk of cardiovascular adverse events among these first-line VEGF inhibitors.
血管内皮生长因子抑制剂，包括酪氨酸激酶抑制剂（TKI）和抗血管生成剂，是治疗晚期和转移性肝细胞癌的一线治疗药物。尽管 TKI 比贝伐珠单抗（抗血管生成剂）具有更大的脱靶不良反应风险，但这两种治疗方法的心血管不良事件风险尚未进行直接比较。
比较接受 TKI（索拉非尼或仑伐替尼）与贝伐珠单抗治疗的肝细胞癌患者心血管不良事件的发生率并对其进行特征描述。
本队列研究纳入了 2018 年 9 月至 2021 年 8 月期间在两家学术医疗中心和一家社区癌症中心接受一线 TKI（索拉非尼或仑伐替尼）或贝伐珠单抗治疗的成年肝细胞癌患者。主要结局为心血管不良事件风险。主要次要结局包括各种类型心血管不良事件的发生率以及与主要不良心血管事件（MACE）相关的危险因素。
研究纳入了 221 名患者（159 名 TKI 患者；62 名贝伐珠单抗患者）。中位随访 5 个月时，两组的心血管不良事件概率无显著差异（风险比[HR]：0.85；95%置信区间[95%CI]：0.58-1.24；p=0.390）。与接受索拉非尼（参照）或贝伐珠单抗治疗的患者相比，接受仑伐替尼治疗的患者心血管事件的累积发生率最高（亚分布风险比[SHR]：1.53；95%CI：1.02-2.30）。在调整了合并症、肝移植状态和基线门静脉血栓形成后，接受 lenvatinib 治疗的患者的心血管不良事件发生率（151 例[68%]）高于接受 sorafenib（105 例[68%]）或 bevacizumab（62 例[100%]）治疗的患者。共观察到 151 例（68%）患者出现心血管不良事件，27 例（12%）患者发生 MACE。与 MACE 相关的危险因素包括高血压（SHR：3.5；95%CI：0.9087-15.83；p=0.086）、既往 MACE 病史（SHR：2.01；95%CI：0.83-4.87；p=0.124）和吸烟史（SHR：2.85；95%CI：0.90-8.97；p=0.074）。
TKI 和贝伐珠单抗之间的心血管风险无显著差异。仑伐替尼似乎是这些一线 VEGF 抑制剂中发生心血管不良事件风险最高的药物。
