Should Propranolol Remain the Gold Standard for Treatment of Infantile Hemangioma? A Systematic Review and Meta-Analysis of Propranolol Versus Atenolol

Abstract

Background: Although propranolol has been established as the gold standard when treatment is sought for infantile hemangioma, concerns over its side effect profile have led to increasing usage of atenolol, a beta-1 selective blocker. Methods: A systematic review of PubMed, Scopus, CINAHL, Google Scholar, and Cochrane was conducted following PRISMA guidelines using MeSH terms and keywords for the terms propranolol, atenolol, and infantile hemangioma, including alternative spellings. All randomized control trials (RCTs) or cohort studies directly comparing outcomes of hemangioma treatment with atenolol and propranolol were included. A meta-analysis with pooled mean differences, pooled odds ratios, and analysis of proportions was performed. Results: A total of 669 participants in 7 studies (3 RCTs and 4 cohort) were included. Propranolol showed a significantly higher rate of complete response compared to atenolol (73.3% vs 85.4%, P = .0004). The pooled mean difference of 0.07 (95% CI –0.12, 0.27) in Hemangioma Activity Score (HAS) was not statistically significant. In terms of side effects, there were significantly more agitation and bronchial hyperreactivity events in the propranolol group ( P = .0245 and P < .0001, respectively). Overall, there was a significantly greater number of adverse events in the propranolol group compared to the atenolol group (185 vs 117, P < .00001). The overall pooled odds ratio was 2.70 (95% CI 1.90, 3.84), indicating that there is 2.7 times higher odds of adverse events in the propranolol group. Conclusion: Propranolol treatment leads to a significantly higher rate of complete response than atenolol. However, its use must be weighed against its greater side effect profile.

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 .…”

Infantile Scalp Hemangiomas: Surgical Management and Lessons Learned

“…Life-threatening complications due to propranolol (bronchospasm, hypotension, bradycardia, hypoglycemia, and ulceration) are rare, but tumor recurrence after termination of treatment is unfortunately common (10%–15%) 1,6,36,39–43 . Other pharmacological agents commonly used in the treatment of IH include other oral beta-blockers (atenolol), topical beta-blockers (timolol), imiquimod, and vincristine 1,5,6,44–47 . Corticosteroids and laser therapy (pulsed dye laser, Nd: YAG 1064 nm laser) may also be utilized but are best employed in conjunction with an oral beta-blocker or as second-line treatment for refractory lesions 46,48–52 …”

“…1,6,36,[39][40][41][42][43] Other pharmacological agents commonly used in the treatment of IH include other oral betablockers (atenolol), topical beta-blockers (timolol), imiquimod, and vincristine. 1,5,6,[44][45][46][47] Corticosteroids and laser therapy (pulsed dye laser, Nd: YAG 1064 nm laser) may also be utilized but are best employed in conjunction with an oral beta-blocker or as second-line treatment for refractory lesions. 46,[48][49][50][51][52] Although excision of IH presents the risk of bleeding due to the vascularity of the tumor, it may be necessary if the lesion is refractory to pharmacological treatment or causing life-threatening sequelae: recurrent bleeding, ulceration, congestive heart failure, or obstruction of a vital structure (airway, ear canal, and visual axis).…”

Comparing the Effectiveness of Propranolol versus Atenolol in Inducing Clinical Clearance in the Treatment of Infantile Haemangioma

“…None of the pre-treatment characteristics proved to be a statistically significant factor in determining the final outcome of the present study. [ 13 ] Castaneda et al . noted that patients who had been started on therapy before five months of age had a significantly better response.…”

“…[ 18 19 20 ] The occurrence of this has been reportedly lower among patients treated with atenolol. [ 13 18 ] Seebauer et al . proposed that the R(+) enantiomers of widely used beta blockers could be repurposed to increase the efficiency of current IH treatment and lower adverse associated side effects.…”