Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, ROC.
Division of Cardiology and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan, ROC.
J Chin Med Assoc. 2024 Jan 1;87(1):48-57. doi: 10.1097/JCMA.0000000000001026. Epub 2023 Nov 22.
Vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) are a common cancer treatment. However, the pharmacologic characteristics of VEGF-TKIs may influence cardiovascular risks. The relative risks of major adverse cardiovascular events (MACEs) associated with VEGF-TKIs are poorly understood.
We searched PubMed, Embase, and ClinicalTrials.gov from inception until August 31, 2021, for phase II/III randomized controlled trials of 11 VEGF-TKIs (axitinib, cabozantinib, lenvatinib, pazopanib, ponatinib, ripretinib, regorafenib, sorafenib, sunitinib, tivozanib, and vandetanib). The endpoints were heart failure, thromboembolism, and cardiovascular death. The Mantel-Haenszel method was used to calculate the risk of VEGF-TKI among users by comparing it to nonusers. Pairwise meta-analyses with a random-effects model were used to estimate the risks of the various VEGF-TKIs. We estimated ranked probability with a P-score and assessed credibility using the Confidence in Network Meta-Analysis framework.
We identified 69 trials involving 30 180 patients with cancer. The highest risk of MACEs was associated with high-potency tivazonib (odds ratio [OR]: 3.34), lenvatinib (OR: 3.26), and axitinib (OR: 2.04), followed by low-potency pazopanib (OR: 1.79), sorafenib (OR: 1.77), and sunitinib (OR: 1.66). The risk of heart failure significantly increased in association with less-selective sorafenib (OR: 3.53), pazopanib (OR: 3.10), and sunitinib (OR: 2.65). The risk of thromboembolism significantly increased in association with nonselective lenvatinib (OR: 3.12), sorafenib (OR: 1.54), and sunitinib (OR: 1.53). Higher potency (tivozanib, axitinib) and lower selectivity (sorafenib, vandetanib, pazopanib, sunitinib) were associated with a higher probability of heart failure. Low selectivity (lenvatinib, cabozantinib, sorafenib, sunitinib) was associated with a higher probability of thromboembolism.
Higher-potency and lower-selectivity VEGF-TKIs may influence the risks of MACEs, heart failure, and thromboembolism. These findings may facilitate evidence-based decision-making in clinical practice.
血管内皮生长因子酪氨酸激酶抑制剂（VEGF-TKIs）是一种常见的癌症治疗方法。然而，VEGF-TKIs 的药理学特性可能会影响心血管风险。与 VEGF-TKIs 相关的主要不良心血管事件（MACEs）的相对风险知之甚少。
我们从 2021 年 8 月 31 日之前的 PubMed、Embase 和 ClinicalTrials.gov 中搜索了 11 种 VEGF-TKIs（axitinib、cabozantinib、lenvatinib、pazopanib、ponatinib、ripretinib、regorafenib、sorafenib、sunitinib、tivozanib 和 vandetanib）的 II/III 期随机对照试验。终点为心力衰竭、血栓栓塞和心血管死亡。采用 Mantel-Haenszel 法比较使用者与非使用者的 VEGF-TKI 风险。采用随机效应模型的成对荟萃分析估计各种 VEGF-TKI 的风险。我们使用 P 评分估计排名概率，并使用置信网络荟萃分析框架评估可信度。
我们确定了 69 项涉及 30180 名癌症患者的试验。高活性 tivozanib（OR：3.34）、lenvatinib（OR：3.26）和 axitinib（OR：2.04）与 MACEs 风险最高，其次是低活性 pazopanib（OR：1.79）、sorafenib（OR：1.77）和 sunitinib（OR：1.66）。与不太选择性的 sorafenib（OR：3.53）、pazopanib（OR：3.10）和 sunitinib（OR：2.65）相比，心力衰竭风险显著增加。与非选择性 lenvatinib（OR：3.12）、sorafenib（OR：1.54）和 sunitinib（OR：1.53）相比，血栓栓塞风险显著增加。更高的效力（tivozanib、axitinib）和更低的选择性（sorafenib、vandetanib、pazopanib、sunitinib）与心力衰竭的可能性更高相关。低选择性（lenvatinib、cabozantinib、sorafenib、sunitinib）与血栓栓塞的可能性更高相关。
更高效力和更低选择性的 VEGF-TKIs 可能会影响 MACEs、心力衰竭和血栓栓塞的风险。这些发现可能有助于临床实践中的循证决策。
