Atherosclerotic cardiovascular disease (ASCVD) affects a substantial proportion of adults with β-thalassaemia. It appears to be driven by conventional CV risk factors rather than disease-specific features, according to research presented at EHA2026.
Advances in treatment have dramatically improved survival among patients with β-thalassaemia, shifting attention towards age-related comorbidities. Although heart disease remains the leading cause of death in this population, the burden of ASCVD has not been well characterised.
Researchers analysed clinical, laboratory, and imaging data from 235 adults with β-thalassaemia receiving care at a tertiary centre in Milan, Italy. The cohort included both transfusion-dependent and non-transfusion-dependent patients, with a median age of 49 years. [EHA 2026, abstract S298]
Overall, 15.7 percent of patients had evidence of ASCVD. Most cases involved atherosclerotic plaques in the carotid, aortic, or femoral arteries. Only a few had experienced a myocardial infarction or an ischaemic brain lesion. As expected, the prevalence of ASCVD increased with age.
Alcohol, smoking, diabetes linked to ASCVD
Traditional CV risk factors were strongly associated with ASCVD. Alcohol consumption, a history of smoking, glucose intolerance, diabetes, and increasing blood pressure were all linked to a significantly increased likelihood of developing atherosclerotic disease.
By contrast, no associations were observed between ASCVD and haemoglobin levels, iron overload, ferritin concentrations, transfusion dependence, or markers of ineffective erythropoiesis. Lipid profiles were also atypical, with most patients having cholesterol levels within or below the normal range, irrespective of ASCVD status. Similarly, endothelial activation markers did not differ between patients with vascular disease and those without.
Need for targeted strategies
“Conventional CV risk factors remain important determinants of ASCVD in ageing patients with β-thalassaemia,” the researchers said. “However, the atypical lipid profile observed in this population suggests that current CV risk assessment tools may be inadequate, highlighting the need to develop thalassaemia-specific approaches to CV risk prediction and prevention.”
While these findings underscore the need for improved CV risk stratification in β-thalassaemia, advances in disease-modifying treatments are also emerging.
Etavopivat a potential new option
In the phase II GLADIOLUS study presented at EHA 2026, the investigational oral pyruvate kinase activator etavopivat increased haemoglobin levels in patients with non-transfusion-dependent thalassaemia α- or β-thalassaemia (NTDT), supporting further investigation in this population. [EHA 2026, abstract S297]
Half of patients experienced a haemoglobin response—an increase of at least 1.0 g/dL from baseline—by week 12, with 39 percent responding by week 24. These improvements persisted through week 48, with least-squares mean changes from baseline of 1.12 g/dL at week 12, 0.88 g/dL at week 24, and 0.91 g/dL at week 48 (p<0.0001 for all).
Markers of ineffective erythropoiesis, haemolysis, and iron metabolism also improved over time. Early and sustained changes in ATP and 2,3-DPG supported etavopivat’s mechanism of action.
Patients with NTDT experience progressive morbidity from chronic anaemia driven by ineffective erythropoiesis and haemolysis, leading to iron overload, organ damage, fatigue, and reduced quality of life.
Etavopivat was well tolerated, with no new safety concerns reported. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity.