Safety confirmation of propranolol use in treatment of infantile hemangiomas
1. In healthy infants, there was no significantly increased risk for cardiovascular or metabolic events associated with propranolol use for treatment of infantile hemangioma. However, there was an increased risk of bronchiolitis.
Evidence Rating Level: 4 (Below Average)
Study Rundown: Infantile hemangiomas are the most common benign tumors of infancy. While the majority of infantile hemangiomas involute by 4 years of age and do not require intervention, hemangiomas complicated by painful ulceration, impaired organ function, and significant disfigurement necessitate systemic therapy. In 2010, oral propranolol was approved for treatment of infantile hemangiomas under a compassionate use protocol by the French Regulatory Agency, which later allowed for standard use in 2014. In this cross-sectional study, researchers evaluated the safety profile of oral propranolol in the treatment of infantile hemangioma using data from a French medico-administrative database. In healthy children who received propranolol, there was no significantly increased risk of developing cardiovascular or metabolic events, however, there was an increased risk of bronchiolitis. In children with underlying disease, there was an increased risk of conduction delays. Limitations of this study include dependence on medical coding, use of medication delivery as a proxy for medication ingestion and clinical events limited to hospitalization only. For providers, this study confirms a good safety profile for use of propranolol in treating infants with infantile hemangioma, with the exception of increased risk of bronchiolitis in healthy children and increased risk of conduction delays in infants with underlying cardiovascular disease.
Relevant Reading: Infantile haemangioma
In-Depth [cross-sectional study]: Researchers analyzed data from the French National Health Insurance database. Inclusion criteria included age <3 years old, care covered by French National Health Insurance, and at least one delivery of propranolol between July 2014 and June 2016. Primary outcomes included hospitalizations secondary to cardiovascular (i.e. conduction disorders, bradycardia, hypotension), respiratory (i.e. reactive airways, bronchospasm), and/or metabolic (i.e. hypoglycemia, hyperkalemia) events. Researchers calculated standard morbidity ratios (SMRs) for the subjects who received propranolol using a reference group (unexposed to propranolol) from the same database, where SMRs are the ratios of observed events to expected events. The study included 1934 children. Of healthy children who received propranolol, there were 2 cardiovascular events (expected = 0.7, SMR = 2.8; 95%CI: 0-6.7), 51 respiratory events (expected = 30.5; SMR = 1.7; 95%CI:1.2-2.1) and 3 metabolic events (expected = 0.6; SMR = 5.1; 95%CI: 0-10.9). Of note, bronchiolitis was the only respiratory event with significantly increased risk (SMR = 1.6; 95%CI: 1.1-2.1). To eliminate confounding, a subanalysis was performed on patients who received hemangiomas with underyling cardiovascular, respiratory, and metabolic disease (n=269). Out of this population, there were 11 cardiovascular events (SMR = 6, 95%CI: 2.5-9.6), 11 respiratory events (SMR = 1.1, 95%CI: 0.5-1.8), and no metabolic events. Of note, conduction delay was the only cardiovascular event with significantly increased risk (SMR = 19; 95%CI: 5.5-31.5) in infants with baseline cardiovascular disease who received propranolol.
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