Noninferiority and Safety of Nadolol vs Propranolol in Infants With Infantile Hemangioma

Abstract

IMPORTANCE Propranolol for infantile hemangiomas (IH) has been shown to be effective and relatively safe. However, other less lipophilic β-blockers, such as nadolol, may be preferable in individuals who experience propranolol unresponsiveness or adverse events. OBJECTIVE To document the noninferiority and safety of oral nadolol compared with oral propranolol in infants with IH.DESIGN, SETTING, AND PARTICIPANTS This double-blind noninferiority prospective study with a noninferiority margin of 10% compared propranolol with nadolol in infants aged 1 to 6 months with problematic IH. The study was conducted in 2 academic pediatric dermatology centers in Canada between 2016 and 2020. Infants aged 1 to 6 months with a hemangioma greater than 1.5 cm on the face or 3 cm or greater on another body part causing or with potential to cause functional impairment or cosmetic disfigurement.INTERVENTIONS Oral propranolol and nadolol in escalating doses up to 2 mg/kg/d. MAIN OUTCOMES AND MEASUREBetween-group differences comparing changes in the bulk (size and extent) and color of the IH at week 24 with baseline using a 100-mm visual analog scale. RESULTSThe study included 71 patients. Of these, 36 were treated with propranolol. The mean (SD) age in this group was 3.1 (1.4) months, and 31 individuals (86%) were female. Thirty-five infants were treated with nadolol. The mean (SD) age in this group was 3.2 (1.6) months, and 26 individuals (74%) were female. The difference in IH between groups by t test was 8.8 (95% CI, 2.7-14.9) for size and 17.1 (95% CI, 7.2-30.0) for color in favor of the nadolol group, demonstrating that nadolol was noninferior to propranolol. Similar differences were noted at 52 weeks: 6.0 (95% CI, 1.9-10.1) and 10.1 (95% CI, 2.9-17.4) for size and color improvement, respectively. For each doubling of time unit (week), the coefficient of involution was 2.4 (95% CI, 0.5-4.4) higher with nadolol compared with propranolol. Safety data were similar between the 2 interventions.CONCLUSIONS AND RELEVANCE Oral nadolol was noninferior to oral propranolol, indicating it may be an efficacious and safe alternative in cases of propranolol unresponsiveness or adverse events, or when faster involution is required.

Transarterial arterial sclerosing embolization for the treatment of propranolol-resistant subglottic hemangioma: Feasibility and effificacy

“…Oral atenolol can be used as an alternative treatment option for IH patients requiring systemic therapy (18). Another randomized controlled trial also showed that oral nadolol was noninferior to oral propranolol, indicating it may be an efficacious and safe alternative in cases of propranolol unresponsiveness or adverse events, or when faster involution is required (19).…”

Practice Variations in Managing Infantile Hemangiomas

“…Ongoing studies continue to demonstrate the safety and efficacy of propranolol as well as other beta-blockers including atenolol, 18,19 nadolol, 20 and topical timolol 21 . Most studies have used a goal dose of 2 to 3 mg/kg/d of propranolol 14 .…”

Beta-blockers in cardiac arrhythmias–Clinical pharmacologist’s point of view

“…An alternative to oral treatment may be patches with propranolol ( Musazzi et al, 2021 ). Nadolol can be an effective and safe alternative to propranolol ( Pope et al, 2022 ). Also in the treatment of subglottic hemangiomas, propranolol and nadolol have been shown to be equally effective ( Yang et al, 2021 ).…”