Sacubitril/Valsartan Comparable to Enalapril in Pediatric Heart Failure, unravels study

The primary objective of the PANORAMA-HF trial was to compare sacubitril/valsartan with enalapril in pediatric HF patients and check whether sacubitril/valsartan was superior to enalapril. The clinical outcomes evaluated were NYHA/Ross classification, patient quality of life, and biomarkers such as NT-proBNP over 52 weeks.

This randomized, double-blind study enrolled 375 children (mean age 8.1±5.6 years, 52% female) with HF due to systemic LVSD. Participants were assigned to either sacubitril/valsartan (N=187) or enalapril (N=188). The first major global rank endpoint evaluated the patients in relation to clinical events, which are mortality, urgent heart transplant listing, requirement of mechanical life support, worsening HF, NYHA/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory. Secondary outcomes involved changes in NT-proBNP levels and safety assessments at 52 weeks.

Key Findings

Clinical Outcomes:

• At 52 weeks, the global rank endpoint did not significantly differ between sacubitril/valsartan and enalapril (Mann-Whitney probability: 0.52, 95% CI: 0.47-0.58, p=0.42).

• Clinically relevant reductions in NYHA/Ross class, PGIS, and Patient Global Impression of Change were seen in both groups.

Biomarkers:

• NT-proBNP levels reduced significantly in both treatment arms, with no meaningful differences between the two.

Safety Profile:

• Adverse events were similar in incidence, 88.8% in the sacubitril/valsartan and 87.8% in the enalapril group.

• The safety profile of sacubitril/valsartan was acceptable in children.

Sacubitril/valsartan was not superior to enalapril in the global rank endpoint in pediatric patients with systemic LVSD. However, both treatments had significant clinical outcomes and quality of life improvements over 52 weeks. The present study showed comparable efficacy and safety of sacubitril/valsartan as an alternative to enalapril in pediatric HF care.

Reference:

Shaddy R, Burch M, Kantor PF, Solar-Yohay S, Garito T, Zhang S, Kocun M, Mao C, Cilliers A, Wang X, Canter C, Rossano J, Wallis G, Menteer J, Daou L, Kusa J, Tokel K, Dilber D, Xu Z, Xiao T, Halnon N, Daly KP, Bock MJ, Zuckerman W, Singh TP, Chakrabarti M, Levitas A, Senni M, Grutter G, Kim GB, Song J, Lee HD, Chen CK, Sanchez-de-Toledo J, Law Y, Wanitkun S, Cui Y, Anjos R, Mese T, Bonnet D; PANORAMA-HF Investigators. Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial. Circulation. 2024 Nov 26;150(22):1756-1766. doi: 10.1161/CIRCULATIONAHA.123.066605. Epub 2024 Sep 25. PMID: 39319469; PMCID: PMC11593999.