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: Annals of Hematology

O. Mulas, G. Caocci, F. Stagno, M. Bonifacio, M. Annunziata, L. Luciano, E.M. Orlandi, E. Abruzzese, N. Sgherza, B. Martino, F. Albano, S. Galimberti, P. Pregno, M. Bocchia, F. Castagnetti, M. Tiribelli, G. Binotto, A. Gozzini, I. Capodanno, C. FozzaD. Luzi, F. Efficace, M.P. Simula, L. Scaffidi, F. De Gregorio, C. Elena, M.M. Trawinska, D. Cattaneo, I. Attolico, C. Baratè, F. Pirillo, A. Sicuranza, G. Gugliotta, R. Stella, E. Scalzulli, A. Iurlo, R. Foà, M. Breccia, G. La Nasa

Research output: Contribution to journalArticlepeer-review

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 3rdG TKIs.

Original languageEnglish
Pages (from-to)1525-1530
Number of pages6
JournalAnn. Hematol.
Volume99
Issue number7
DOIs
Publication statusPublished - 2020

Keywords

  • Arterial occlusive events
  • Chronic myeloid leukemia
  • Hypertension
  • Renin angiotensin system inhibitors
  • TKI
  • angiotensin receptor antagonist
  • antihypertensive agent
  • BCR ABL protein
  • beta adrenergic receptor blocking agent
  • bosutinib
  • dasatinib
  • dipeptidyl carboxypeptidase inhibitor
  • doxazosin
  • nilotinib
  • ponatinib
  • protein tyrosine kinase inhibitor
  • thiazide diuretic agent
  • protein kinase inhibitor
  • adult
  • aged
  • angina pectoris
  • aortic aneurysm
  • artery occlusion
  • artery thrombosis
  • Article
  • cardiomyopathy
  • cerebrovascular accident
  • chronic myeloid leukemia
  • controlled study
  • diabetes mellitus
  • drug efficacy
  • drug safety
  • dyslipidemia
  • female
  • heart arrhythmia
  • heart failure
  • heart infarction
  • human
  • hypertension
  • incidence
  • kidney failure
  • major clinical study
  • male
  • platelet count
  • priority journal
  • renin angiotensin aldosterone system
  • risk factor
  • scoring system
  • smoking
  • Systematic Coronary Risk Evaluation
  • systolic blood pressure
  • valvular heart disease
  • classification
  • cohort analysis
  • combination drug therapy
  • complication
  • drug effect
  • middle aged
  • survival analysis
  • thrombosis
  • very elderly
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Humans
  • 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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