PANORAMA-HF
Trial question
What is the role of sacubitril/valsartan in children with HF attributable to systemic LV systolic dysfunction?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
51.0% female
49.0% male
N = 375
375 patients (193 female, 182 male).
Inclusion criteria: children with HF attributable to systemic LV systolic dysfunction.
Key exclusion criteria: single ventricle physiology; systemic morphologic right ventricle; restrictive cardiomyopathy; HCM.
Interventions
N=187 sacubitril/valsartan (target dose of 2.3-3.1 mg/kg BID).
N=188 enalapril (target dose of 0.2 mg/kg BID with a maximum dose of 10 mg BID).
Primary outcome
Global rank end point (consisting of ranking patients from worst to best on basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening heart failure, New York Heart Association/Ross class, Patient Global Impression of Severity, and Pediatric Quality of Life Inventory physical functioning domain) at week 52
50%
45.1%
50.0 %
37.5 %
25.0 %
12.5 %
0.0 %
Sacubitril/valsartan
Enalapril
No significant
difference ↔
No significant difference in global rank end point (consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, NYHA/Ross class, Patient Global Impression of Severity, and Pediatric QoL Inventory physical functioning domain) at week 52 (50% vs. 45.1%; OR 0.91, 95% CI 0.72 to 1.14).
Secondary outcomes
No significant difference in time to first positively adjudicated category 1 or 2 events (including death, requirement of listing for an urgent heart transplant, requirement for mechanical circulatory or respiratory support, worsening HF with or without ICU or general ward hospitalization) at week 52 (18.2% vs. 17.6%; HR 1.07, 95% CI 0.66 to 1.72).
No significant difference in clinically relevant improvement in NYHA/Ross functional class at week 52 (37.7% vs. 34%; OR 1.1, 95% CI 0.7 to 1.7).
No significant difference in improvement in patient-reported Pediatric QoL total score at week 52 (4.8 points vs. 1.7 points; MD 3.1, 95% CI -0.8 to 7).
Safety outcomes
No significant difference in adverse and serious adverse events.
Conclusion
In children with HF attributable to systemic LV systolic dysfunction, sacubitril/valsartan was not superior to enalapril with respect to global rank end point (consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, NYHA/Ross class, Patient Global Impression of Severity, and Pediatric QoL Inventory physical functioning domain) at week 52.
Reference
Robert Shaddy, Michael Burch, Paul F Kantor et al. Sacubitril / Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial. Circulation. 2024 Nov 26;150(22):1756-1766.
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