Matsumura Itaru
Kindai University Faculty of Medicine, Department of Hematology & Rheumatology.
Rinsho Ketsueki. 2018;59(1):13-26. doi: 10.11406/rinketsu.59.13.
Tyrosine kinase inhibitors (TKIs) have significantly improved the clinical outcomes of patients with chronic myeloid leukemia (CML). However, patients with CML need to receive TKI therapy for several years. Hence, the safety of long-term TKI treatment warrants utmost attention. Among various adverse events caused by TKI therapy, cardiovascular events (CVEs), such as acute myocardial infarction, cerebral infarction, and pulmonary hypertension, are the most serious with high mortality. TKIs inhibit various off-target molecules involved in the occurrence of CVEs such as c-Kit, platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor (VEGFR), and Tie-2/Tec. At present, nilotinib, dasatinib, and ponatinib, but not bosutinib, have been demonstrated to increase the risk of CVEs in patients with CML compared with imatinib. Conversely, patients with CML have also been shown to have high CVE risks regardless of the TKI treatment compared with non-cancer population. Hence, further analyses are required to deduce the influence of TKI treatment on CVEs. Whatever the cause may be, to prevent CVEs in patients with CML, we need to appropriately screen and monitor CVE risks such as hypertension, serum glucose, lipid levels, ankle-brachial index (ABI), Electrocardiography (ECG), and echocardiography before and during TKI treatment.
酪氨酸激酶抑制剂（TKIs）显著改善了慢性髓性白血病（CML）患者的临床结局。然而，CML患者需要接受数年的TKI治疗。因此，长期TKI治疗的安全性值得高度关注。在TKI治疗引起的各种不良事件中，心血管事件（CVEs），如急性心肌梗死、脑梗死和肺动脉高压，最为严重，死亡率很高。TKIs抑制参与CVEs发生的各种脱靶分子，如c-Kit、血小板衍生生长因子受体（PDGFR）、血管内皮生长因子受体（VEGFR）和Tie-2/Tec。目前，与伊马替尼相比，尼洛替尼、达沙替尼和波纳替尼（而非博舒替尼）已被证明会增加CML患者发生CVEs的风险。相反，与非癌症人群相比，无论是否接受TKI治疗，CML患者也被证明具有较高的CVEs风险。因此，需要进一步分析以推断TKI治疗对CVEs的影响。无论原因如何，为预防CML患者发生CVEs，我们需要在TKI治疗前和治疗期间适当筛查和监测CVEs风险，如高血压、血糖、血脂水平、踝臂指数（ABI）、心电图（ECG）和超声心动图。
