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Sacubitril/Valsartan in Pediatric HF (PANORAMA-HF Trial)
Quick Takes
- Sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to LV systolic dysfunction using a prespecified global rank endpoint.
- Both treatment arms showed clinically meaningful improvements over 52 weeks.
Study Questions:
What is the safety and efficacy of sacubitril/valsartan as compared with enalapril in children 1 month to <18 years of age with heart failure (HF) attributable to systemic left ventricular (LV) dysfunction?
Methods:
An international, multicenter prospective, randomized, double-blind study was performed. Patients with HF, biventricular cardiac physiology, and systemic LV dysfunction were included. Patients with single ventricle physiology, restrictive cardiomyopathy, systemic morphologic right ventricle, and hypertrophic cardiomyopathy were excluded. Patients were randomized to receive either sacubitril/valsartan or enalapril. The primary outcome was a primary global rank endpoint ranking patients from worst to best on the basis of clinical events such as death, urgent listing for transplant, mechanical circulatory support, worsening HF, New York Heart Association (NYHA)/Ross functional class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain.
Results:
A total of 375 children (mean age 8.1 ± 5.6 years; 52% female) were randomized, 187 to sacubitril/valsartan, and 188 to enalapril. At week 52, no significant difference was observed between the two treatment arms in the primary endpoint (Mann-Whitney probability, 0.52 [95% CI, 0.47-0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72-1.14]; p = 0.42). Both enalapril and sacubitril/valsartan led to clinically meaningful reductions in NYHA/Ross, PGIS, Patient Global Impression of Change, and N-terminal pro–B-type natriuretic peptide (NT-proBNP), without significant differences between therapies. Adverse events were similar between groups.
Conclusions:
The authors conclude that sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to LV systolic dysfunction using the prespecified global rank endpoint.
Perspective:
This exceedingly well-designed and executed study is destined to be quoted on pediatric cardiology rounds for many years to come. Studies of therapies for pediatric HF are challenging because of small patient numbers, a heterogeneous patient population, and lack of validated clinical efficacy endpoints. This study clearly took advantage of lessons learned from previous studies in pediatric HF and enrolled a relatively homogenous group of patients with LV systolic dysfunction and used a robust composite endpoint.
The obvious question is to why there is a discrepancy in the adult studies and this pediatric study. The answer to this is not entirely clear. One possible explanation is that the pediatric population is a different group of patients with different event rates than adults, and this study was powered for a different outcome. While it is possible that an even larger study may have demonstrated a difference, such a study is unlikely to be feasible. This study is likely to provide the most definitive data available. Importantly, both sacubitril/valsartan and enalapril showed benefit in pediatric patients with LV dysfunction.
Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure, Congenital Heart Disease and Pediatric Cardiology
Keywords: Heart Failure, Pediatrics, Ventricular Dysfunction, Left
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