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(G) TKIs.

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

Bonifacio, Massimiliano;Scaffidi, Luigi;
2020

Abstract

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(G) TKIs.
Arterial occlusive events
Chronic myeloid leukemia
Hypertension
Renin angiotensin system inhibitors
TKI
Adult
Aged
Aged, 80 and over
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Cohort Studies
Drug Therapy, Combination
Female
Humans
Hypertension
Incidence
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Male
Middle Aged
Protein Kinase Inhibitors
Renin-Angiotensin System
Risk Factors
Survival Analysis
Thrombosis
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1029204
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