Extrapolation of Adult Evidence to Pediatric Practice: Bridging the Gap in Pediatric Heart Failure Pharmacotherapy

Heart failure (HF) is a complex clinical syndrome that represents an increasingly relevant health issue, associated with substantial morbidity and mortality in pediatric patients. While considerable therapeutic advances have transformed the prognosis of adult patients with heart failure over the past three decades, progress in pediatric heart failure has been considerably slower. In adult patients, large randomized controlled trials (RCTs) have established angiotensin-converting enzyme inhibitors (ACE inhibitors), beta-blockers, mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and, more recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors as the cornerstone of guideline-directed medical therapy. Evidence supporting pharmacological therapy in pediatric heart failure remains scarce and frequently inconclusive, with most available studies being limited by small sample sizes and heterogeneous patient populations. Therefore, heart failure treatment in children is mostly extrapolated from adult studies and guidelines. However, developmental differences in myocardial structure and function, neurohormonal signaling, pharmacokinetics and pharmacodynamics may substantially influence therapeutic response. In addition, the rarity and the etiological heterogeneity of pediatric HF create major methodological challenges for adequately powered clinical trials. This review compares the pharmacological management of HF in adult and pediatric populations, examines the strength of evidence for contemporary therapies and discusses the biological and methodological limitations of translating adult evidence into pediatric practice. Multicenter collaborative studies and well-designed pediatric randomized controlled trials are essential for establishing truly evidence-based pharmacological strategies for children with HF.