Les complications cardiovasculaires liées aux inhibiteurs BTK dans les hémopathies lymphoïdes malignes

Details

Supervisors

Vellemans, Hélène

Faculty

Faculté de médecine et médecine dentaire

Degree label

Master [180] en médecine, à finalité spécialisée

Abstract

enIntroduction: Bruton’s tyrosine kinase (BTK), discovered in 1952 by Ogden Bruton during his research on X-linked agammaglobulinemia (XLA), plays a role in the proliferation, maturation, and survival of B lymphocytes. The introduction of the first BTK inhibitor, ibrutinib, approved by the FDA in 2013, revolutionized the management of malignant lymphoid hemopathies. However, despite their therapeutic efficacy, these agents have been associated with significant cardiovascular adverse effects, including episodes of atrial fibrillation, arterial hypertension, bleeding, and heart failure. Objective: The primary objective of this study was to assess the incidence of cardiovascular complications in patients with malignant lymphoid hemopathies treated with BTK inhibitors at CHU UCL Namur. The secondary objectives were to compare the risk profiles of patients who experienced cardiovascular events with those who did not, and to evaluate the association between high HFA-ICOS and HAS-BLED scores and the occurrence of cardiovascular events. Methods and statistical analysis: A retrospective study was conducted on a cohort of 69 patients treated with BTK inhibitors since their introduction in the hematology department of CHU UCL Namur. The incidence of cardiovascular events under BTK inhibitor therapy was calculated by relating the number of observed events to the total number of treated patients. Comparisons between groups (with and without cardiovascular events) were performed using the Chi-square test or Fisher’s exact test for qualitative variables, and the Mann–Whitney test for quantitative variables.HFA-ICOS and HAS-BLED scores were calculated for each patient. A comparison between the two patient groups was carried out to evaluate the association between these scores and the occurrence of cardiovascular complications during BTK inhibitor therapy. Results: The incidence of cardiovascular complications was 58% (95% CI: 45%–70%), with a bleeding incidence of 22% (95% CI: 13%–24%), arterial hypertension of 19% (95% CI: 11%–30%), atrial fibrillation of 16% (95% CI: 8.6%–27%), and heart failure of 7.2% (95% CI: 2.7%–17%). No statistically significant difference was observed between the groups (with and without cardiovascular events) for demographic and clinical factors (sex, age, body mass index, smoking, dyslipidemia, arterial hypertension, cardiovascular history). Although the HAS-BLED and HFA-ICOS scores showed certain trends, particularly for atrial fibrillation with HFA-ICOS (p = 0.076), no significant association was established between high predictive scores and the occurrence of complications. Conclusion: This study reveals a high incidence (58%) of cardiovascular complications during BTK inhibitor therapy. However, neither traditional cardiovascular risk factors nor the HAS-BLED and HFA-ICOS scores demonstrated sufficient reliability in predicting the occurrence of these complications. These results highlight the need to explore other markers or approaches to better assess cardiovascular risk in this population.