Renin angiotensin system inhibitors reduce the incidence of arterial thrombotic events in patients with hypertension and chronic myeloid leukemia treated with second- or third-generation tyrosine kinase inhibitors

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 3rdG TKIs.

Keywords: Arterial occlusive events; Chronic myeloid leukemia; Hypertension; Renin angiotensin system inhibitors; TKI.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / epidemiology
  • Incidence
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / complications
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / epidemiology
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / classification
  • Protein Kinase Inhibitors / therapeutic use*
  • Renin-Angiotensin System / drug effects
  • Risk Factors
  • Survival Analysis
  • Thrombosis / epidemiology*
  • Thrombosis / prevention & control


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Protein Kinase Inhibitors