Cardiovascular risk and disease in haemophilia a patients: the comor-HA cohort study
M Erard, L Bommarez, M Jeurissen, P Verhamme, C Hermans, Q Van Thillo, T VanasscheAbstract
Introduction
– Haemophilia A is a congenital bleeding disorder, which can be treated with factor VIII (FVIII) products and emicizumab, a bispecific monoclonal antibody mimicking endogenous factor VIII. These advances in prophylactic and on-demand haemostatic therapies have dramatically increased life expectancy in haemophilia patients, exposing them to age-related comorbidities including atherosclerotic cardiovascular (CV) disease. Despite the partial normalisation of haemostasis by emicizumab, it has historically been associated with thrombotic adverse events. Therefore, there is a need to better characterise CV risk factors and events in the ageing haemophilia patients in general, including those being treated with emicizumab.
Purpose
– This cohort study aims to characterise CV comorbidities and events in haemophilia A patients treated with emicizumab or FVIII therapy.
Methods
– This retrospective multicentre study included 105 patients with severe haemophilia A, aged 40 years or older during the study period from January 2020 till December 2024. We collected patient characteristics, subclinical CV markers, number of bleeding and CV events (atrial fibrillation, ischaemic stroke, myocardial infarction, venous thromboembolism), and antithrombotic practices post-events. CV risk factor prevalence was compared with the general Belgian population using Sciensano epidemiological data via a Fisher exact test.
Results
– Within this cohort, 99 (94.3%) patients were treated with emicizumab. The median age was 57 (IQR 49-65). Smoking was significant more prevalent in haemophilia patients than in the general Belgian population (current smokers 27.4% vs 15.6% [p=0.001], former smokers 32.6% vs 28.3% [p=0.001]). Individuals with haemophilia were more likely to have arterial hypertension (AHT) and dyslipidaemia compared to the general population and these differences were most pronounced in the age group of 40-65 years (AHT 70.4% vs 23.6% [p<0.001], dyslipidaemia 50.0% vs 34.8% [p=0.005]). The mean body mass index (BMI) was 26.5 (95% CI 25.6-27.4), which was not different from the general Belgian population. During the study period, there were 4 CV events (2 atrial fibrillation cases, 1 subsegmental pulmonary embolism case and 1 acute anterior ST-segment elevation myocardial infarction [STEMI] case).
Conclusion
– This retrospective cohort study represents the largest available source of information on real-world emicizumab use in Belgium and enables granular CV risk profiling under therapeutic emicizumab using an unbiased approach by evaluating all patients with haemophilia above 40 years. More prospective research is needed to further unravel the prevalence of CV risk and disease in the haemophilia population and to identify tailored antithrombotic therapy regimens following a CV event.