How much aspirin do children with heart disease need?

Children with congenital and chronic heart disease have a high risk of arterial thrombosis, which can be reduced by aspirin. However, the optimal dose for pediatric patients remains largely unclear.

Aspirin for thrombosis prophylaxis in children with heart disease

Aspirin has a broad range of indications for infants and children with congenital and acquired heart disease.
Although the antiplatelet drug is frequently used in these patients, data on the correct dosage are limited.
In particular, little is known about the effect of aspirin in stable, outpatient pediatric patients.
Most treatment guidelines recommend the lowest effective dose between 1 and 5 mg/kg/day to prevent thrombotic complications.

Division into different dose and age groups

For their study, Irish researchers from Dublin recruited 105 patients aged 18 years and younger from cardiology outpatient clinics. The patients suffered from various congenital or acquired heart diseases that required aspirin therapy. The most common diagnoses were hypoplastic left heart syndrome (45.5%), tetralogy of Fallot, and cardiomyopathy (8.9% each).

Patients were divided into four quartiles based on aspirin dose:

Q1: 1.12–1.97 mg/kg/day
Q2: 2.03–2.91 mg/kg/day
Q3: 3.0–3.91 mg/kg/day
Q4: >4.17 mg/kg/day

Stratification was also performed by age, with the primary focus being on the two age groups under and over 2 years.

Two in vitro tests commonly used in pediatric cardiology patients, thromboelastography and platelet light transmission aggregometry (PRP), were used to determine platelet aggregation, with cutoffs for non-response and partial response, respectively.

Varying Response Depending on Dose and Age

Among patients under 2 years of age, all responded to treatment with the highest aspirin dose (Q4). There were two non-responders in Q2 and Q3, and two semi-responders in Q2. No patient in this age group received a low dose of 1.12 to 1.97 mg/kg/day. The most common diagnoses among non- and semi-responders were truncus arteriosus, tetralogy of Fallot, and hypoplastic left heart syndrome. However, no general association between the primary diagnosis and response to aspirin could be established.

The same was true for the age group over 2 years, where those who did not respond optimally had transposition of the great arteries or hypoplastic left heart syndrome. In contrast to the younger children, all responded to aspirin in both Q4 and Q3, with no significant difference between the two doses. In Q1 and Q2, there were a number of semi- and non-responders, with response in these dose groups varying greatly between 100% platelet inhibition and no inhibition at all.

Impending under- or overtreatment with aspirin

The authors drew the following conclusions from the study:

Overall, response to aspirin varies greatly depending on the dose and age of the patients. A clear relationship between diagnosis and treatment response could not be established.
Younger children < 2 years of age tend to require higher doses for effective platelet inhibition, possibly 5 mg/kg/day.
For children > 2 years of age, a dosage of 3 mg/kg/day may be sufficient, as all children responded to treatment below this dose.
Current practice may lead to reduced platelet inhibition in some children due to underdosing and to overdosing in others. Therefore, increased laboratory monitoring should be performed.

Source:

Regan, IE et al. The Effects of Aspirin dose in Children with Congenital and Acquired Heart Disease. Results from the Paediatric Study of Aspirin Efficacy using Diagnostic and Monitoring Tools (PAED-M). Pediatr Cardiol (2024). https://doi.org/10.1007/s00246-024-03509-6.