Mulas Olga, Caocci Giovanni, Mola Brunella, La Nasa Giorgio
Hematology Unit, Businco Hospital, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Front Pharmacol. 2021 Sep 22;12:674748. doi: 10.3389/fphar.2021.674748. eCollection 2021.
Off-target effects in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) are associated with cardiovascular toxicity. Hypertension represents an important cardiovascular complication and, if not appropriately managed, can contribute to developing thrombotic events. Third-generation TKI ponatinib is associated with hypertension development, and its use is more restricted than in the past. Few data are reported for second-generation TKI, nilotinib, dasatinib, and bosutinib. The aim of this article was to evaluate with a systematic review and meta-analysis the real incidence of hypertension in CML patients treated with second- or third-generation TKI. The PubMed database, Web of Science, Scopus, and ClinicalTrials.gov were systematically searched for studies published between January 1, 2000, and January 30, 2021; the following terms were entered in the database queries: Cardiovascular, Chronic Myeloid Leukemia, CML, Tyrosine kinases inhibitor, TKI, and Hypertension. The study was carried out according to the Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) statement. A pooled analysis of hypertension incidence was 10% for all new-generation TKI, with an even higher prevalence with ponatinib (17%). The comparison with the first-generation imatinib confirmed that nilotinib was associated with a significantly increased risk of hypertension (RR 2; 95% CI; 1.39-2.88, I=0%, z=3.73, p=0.0002). The greatest risk was found with ponatinib (RR 9.21; 95% CI; 2.86-29.66, z=3.72, p=0.0002). Hypertension is a common cardiovascular complication in CML patients treated with second- or third-generation TKI.
接受酪氨酸激酶抑制剂（TKIs）治疗的慢性粒细胞白血病（CML）患者的脱靶效应与心血管毒性相关。高血压是一种重要的心血管并发症，若管理不当，可导致血栓形成事件。第三代TKI波纳替尼与高血压的发生有关，其使用比过去受到更多限制。关于第二代TKI尼罗替尼、达沙替尼和博舒替尼的相关数据报道较少。本文旨在通过系统评价和荟萃分析评估接受第二代或第三代TKI治疗的CML患者高血压的实际发生率。对PubMed数据库、科学网、Scopus和ClinicalTrials.gov进行系统检索，以查找2000年1月1日至2021年1月30日期间发表的研究；在数据库查询中输入以下术语：心血管、慢性粒细胞白血病、CML、酪氨酸激酶抑制剂、TKI和高血压。该研究按照系统评价和荟萃分析的首选报告项目（PRISMA）声明进行。所有新一代TKI的高血压发生率汇总分析为10%，波纳替尼的患病率更高（17%）。与第一代伊马替尼的比较证实，尼罗替尼与高血压风险显著增加相关（RR 2；95% CI；1.39 - 2.88，I = 0%，z = 3.73，p = 0.0002）。波纳替尼的风险最高（RR 9.21；95% CI；2.86 - 29.66，z = 3.72，p = 0.0002）。高血压是接受第二代或第三代TKI治疗的CML患者常见的心血管并发症。
