Long-Term Prophylactic Effect of Angiotensin Receptor Blockers in Children with Genetic Aortopathies: The Early Bird Catches the Worm

Background: Genetic aortopathies (GA) manifest with various extracardiac as well as cardiac symptoms. Particular attention is paid to the dilatation of the aortic root which has major impact on morbidity and mortality. Some trials have been conducted in children and showed similar effectiveness of angiotensin receptor blockers (ARB) and beta-blockers (BB). This study focuses on the long term effect of therapy with ARB and/or BB on aortic root growth and the question which of the drugs to choose as first line therapy at different ages.

Method: Since 1998, we diagnosed 203 patients with GA (165 FBN1, 19 LDS, 19 others). Eighty-two patients between 3 months and 16 years receiving either ARB or BB therapy were included in this study. We retrospectively analyzed the progression of the dilatation of sinus Valsalva (SV) using calculated z-scores before and after therapy initiation and compared BB and ARB treatment in detail.

Results: This study proved that both ARB and BB (p < 0.05) therapy showed significant benefit by reducing the growth of the aortic root, while the effect is significantly more pronounced in ARB (p < 0.01) independent of age and genetic causes. A detailed comparison of the two drug groups showed a more sustained effect in limiting the progression of the dilatation of the aortic root in patients treated with ARB. Long-term progression of dilatation of the SV was significantly lower in children treated with ARBs compared to BB (delta Z-score, p < 0.05). In addition, ARB were better tolerated overall and had a significant lower discontinuation rate (3%) compared to beta-blockers (53%) (p < 0.001). Independently of the age at initiation of prophylaxis, all children and adolescents were able to reach the target dose under ARB.

Conclusion: In our cohort we demonstrate a significant benefit with both treatment options, but the effect was more pronounced and longer lasting in ARB. In contrast to beta-blockers a very good tolerance of the medication was observed in ARB making it our therapy of choice in children and adolescents. As a next step it would be important to define what dose to start with and which target dose to reach. At this point, it is no longer a question of which medication we use but in which dosage and at what time.

Publication History

Article published online:
28 January 2023