Department of Medical Sciences and Public Health, University of Cagliari, Hematology Businco Hospital, Cagliari, Italy.
SC Ematologia e CTMO, Ospedale Businco, Dipartimento di Scienze Mediche e Sanità Pubblica, Università di Cagliari, Via Jenner, sn, 09124, Cagliari, Italy.
Ann Hematol. 2020 Jul;99(7):1525-1530. doi: 10.1007/s00277-020-04102-6. Epub 2020 May 30.
Hypertension is a commonly reported comorbidity in patients diagnosed with chronic myeloid leukemia (CML), and its management represents a challenge in patients treated with 2nd- or 3rd-generation tyrosine kinase inhibitors (TKIs), considering their additional cardiovascular (CV) toxicity. The renin angiotensin system (RAS) contributes to hypertension genesis and plays an important role in atherosclerosis development, proliferation, and differentiation of myeloid hematopoietic cells. We analyzed a cohort of 192 patients with hypertension at CML diagnosis, who were treated with 2nd- or 3rd-generation TKIs, and evaluated the efficacy of RAS inhibitors (angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARBs)) in the prevention of arterial occlusive events (AOEs), as compared with other drug classes. The 5-year cumulative incidence of AOEs was 32.7 ± 4.2%. Patients with SCORE ≥ 5% (high-very-high) showed a significantly higher incidence of AOEs (33.7 ± 7.6% vs 13.6 ± 4.8%, p = 0.006). The AOE incidence was significantly lower in patients treated with RAS inhibitors (14.8 ± 4.2% vs 44 ± 1%, p < 0.001, HR = 0.283). The difference in the low and intermediate Sokal risk group was confirmed but not in the high-risk group, where a lower RAS expression has been reported. Our data suggest that RAS inhibitors may represent an optimal treatment in patients with hypertension and CML, treated with 2nd or 3rd TKIs.
高血压是慢性髓性白血病(CML)患者常见的合并症,由于第二代或第三代酪氨酸激酶抑制剂(TKI)具有额外的心血管毒性,其管理对接受这些药物治疗的患者构成挑战。肾素血管紧张素系统(RAS)参与高血压的发生,在动脉粥样硬化的发展、髓系造血细胞的增殖和分化中发挥重要作用。我们分析了 192 例 CML 诊断时患有高血压的患者队列,他们接受了第二代或第三代 TKI 治疗,并评估了 RAS 抑制剂(血管紧张素转换酶抑制剂(ACEi)和血管紧张素 II 受体阻滞剂(ARB))在预防动脉闭塞性事件(AOEs)方面的疗效,与其他药物类别相比。AOEs 的 5 年累积发生率为 32.7%±4.2%。SCORE≥5%(高-极高)的患者 AOE 发生率明显更高(33.7%±7.6% vs 13.6%±4.8%,p=0.006)。与接受其他药物治疗的患者相比,接受 RAS 抑制剂治疗的患者 AOE 发生率明显更低(14.8%±4.2% vs 44%±1%,p<0.001,HR=0.283)。低危和中危 Sokal 风险组的差异得到了证实,但高危组没有得到证实,因为有报道称高危组的 RAS 表达较低。我们的数据表明,RAS 抑制剂可能代表高血压和 CML 患者的最佳治疗选择,这些患者接受第二代或第三代 TKI 治疗。