Cirmi Santa, El Abd Asmae, Letinier Louis, Navarra Michele, Salvo Francesco
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, I-98168 Messina, Italy.
Inserm, UMR 1219, Team Pharmacoepidemiology, Bordeaux Population Health Research Center, University of Bordeaux, F-33000 Bordeaux, France.
Cancers (Basel). 2020 Mar 30;12(4):826. doi: 10.3390/cancers12040826.
Tyrosine kinase inhibitors (TKIs), the treatment of choice for chronic myeloid leukemia (CML), can be associated to cardiovascular (CV) adverse events (AEs). A case/non-case study was performed using AE reports registered in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to compare the risk of CV event reports related to TKIs indicated in the management of chronic myeloid leukemia (CML). Disproportionality of CV event-related TKIs was computed using the Reporting Odds Ratio (ROR) as a measure of potential risk increase. Nilotinib accounts for more than half of reported cases related to TKIs. Signal of Disproportionate Reporting (SDR) was found for cardiac failure, ischemic heart disease, cardiac arrhythmias, /QT prolongation, hypertension, and pulmonary hypertension. Dasatinib and bosutinib were related to the highest disproportionality for cardiac failure. Nilotinib was associated with the highest SDR for ischemic heart disease, /QT prolongation and cardiac arrhythmias. Only ponatinib was related to an SDR for hypertension, while dasatinib and imatinib were related to pulmonary hypertension. In the context of CML, TKIs have different safety profiles related to CV events, among which nilotinib seems particularly related to. These results claim for a revision of its CV safety profile mainly for the risk of /QT prolongation.
酪氨酸激酶抑制剂（TKIs）是慢性髓性白血病（CML）的首选治疗药物，可能与心血管（CV）不良事件（AEs）相关。利用美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）数据库中登记的不良事件报告进行了一项病例/非病例研究，以比较慢性髓性白血病（CML）管理中所使用的TKIs相关的CV事件报告风险。使用报告比值比（ROR）作为潜在风险增加的衡量指标，计算与CV事件相关的TKIs的不成比例性。尼洛替尼占与TKIs相关报告病例的一半以上。发现心力衰竭、缺血性心脏病、心律失常、QT间期延长、高血压和肺动脉高压存在不成比例报告信号（SDR）。达沙替尼和博舒替尼与心力衰竭的最高不成比例性相关。尼洛替尼与缺血性心脏病、QT间期延长和心律失常的最高SDR相关。仅波纳替尼与高血压的SDR相关，而达沙替尼和伊马替尼与肺动脉高压相关。在CML的背景下，TKIs与CV事件相关的安全性概况不同，其中尼洛替尼似乎与之特别相关。这些结果要求对其CV安全性概况进行修订，主要针对QT间期延长的风险。
