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.
Olga MulasGiovanni CaocciFabio StagnoMassimiliano BonifacioMario AnnunziataLuigiana LucianoEster Maria OrlandiElisabetta AbruzzeseNicola SgherzaBruno MartinoFrancesco AlbanoSara GalimbertiPatrizia PregnoMonica BocchiaFausto CastagnettiMario TiribelliGianni BinottoAntonella GozziniIsabella CapodannoClaudio FozzaDebora LuziFabio EfficaceMaria Pina SimulaLuigi ScaffidiFiorenza De GregorioChiara ElenaMalgorzata Monika TrawinskaDaniele CattaneoImma AttolicoClaudia BaratèFrancesca PirilloAnna SicuranzaGabriele GugliottaRossella StellaEmilia ScalzulliAlessandra IurloRobin FoàMassimo BrecciaGiorgio La NasaPublished in: Annals of hematology (2020)
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.
Keyphrases
- chronic myeloid leukemia
- angiotensin converting enzyme
- angiotensin ii
- blood pressure
- risk factors
- wild type
- newly diagnosed
- cardiovascular disease
- vascular smooth muscle cells
- bone marrow
- type diabetes
- end stage renal disease
- ejection fraction
- induced apoptosis
- poor prognosis
- signaling pathway
- emergency department
- dendritic cells
- immune response
- machine learning
- arterial hypertension
- acute myeloid leukemia
- patient reported outcomes
- peritoneal dialysis
- big data
- deep learning
- sickle cell disease