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Efficacy and Safety of Propranolol vs Atenolol in Infants With Problematic Infantile HemangiomasA Randomized Clinical Trial

Educational Objective
To compare the efficacy and safety of orally administered propranolol vs atenolol in treating potentially disfiguring or functionally threatening infantile hemangiomas.
1 Credit CME
Key Points

Question  In light of the positive efficacy and safety of atenolol, can it be used as a promising therapy for infantile hemangiomas?

Findings  In this randomized clinical trial of 377 patients with infantile hemangiomas, the response rate and hemangioma activity score after 6 months of treatment were similar in the propranolol and atenolol groups. Adverse events were more common in the propranolol group than the atenolol group.

Meaning  Atenolol can be considered a first-line treatment for infantile hemangiomas.


Importance  Propranolol has become the first-line therapy for problematic infantile hemangiomas (IHs) that require systemic therapy. However, different adverse events have been reported during propranolol treatment. The positive efficacy and safety of atenolol raise the question of whether it could be used as a promising therapy for IH.

Objective  To compare the efficacy and safety of propranolol vs atenolol in infants (between age 5 and 20 weeks) with problematic IHs who required systemic therapy.

Design, Setting, and Participants  This was a prospective, multicenter, randomized, controlled, open-label clinical trial conducted in collaboration among 6 separate investigation sites in China from February 1, 2015, to December 31, 2018. A total of 377 patients met the criteria for inclusion and were randomized to the propranolol (190 [50.4%]) and atenolol (187 [49.6%]) groups. Data were analyzed in June 2020.

Interventions  Participants were randomized to receive either propranolol or atenolol for at least 6 months. They completed efficacy assessments at 2 years after the initial treatment.

Main Outcomes and Measures  The primary outcome was any response or nonresponse at 6 months. The key secondary outcome was changes in the hemangioma activity score.

Results  Of 377 participants, 287 (76.1%) were female, and the mean (SD) age was 10.2 (4.0) weeks in the propranolol group and 9.8 (4.1) weeks in the atenolol group. After 6 months of treatment, in the propranolol and atenolol groups, the overall response rates were 93.7% and 92.5%, respectively (difference, 1.2%; 95% CI, −4.1% to 6.6%). At 1 and 4 weeks after treatment, and thereafter, the hemangioma activity score in the atenolol group aligned with the propranolol group (odds ratio, 1.034; 95% CI, 0.886-1.206). No differences between the propranolol group and atenolol group were observed in successful initial responses, quality of life scores, complete ulceration healing times, or the rebound rate. Both groups presented a similar percentage of complete/nearly complete responses at 2 years (82.1% vs 79.7%; difference, 2.4%; 95% CI, −5.9% to 10.7%). Adverse events were more common in the propranolol group (70.0% vs 44.4%; difference, 25.6%; 95% CI, 15.7%-34.8%), but the frequency of severe adverse events did not differ meaningfully between the groups.

Conclusions and Relevance  In this randomized clinical trial, when compared with propranolol, atenolol had similar efficacy and fewer adverse events in the treatment of infants with problematic IHs. The results suggest that oral atenolol can be used as an alternative treatment option for patients with IH who require systemic therapy.

Trial Registration  ClinicalTrial.gov Identifier: NCT02342275

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: February 23, 2021.

Published Online: April 15, 2021. doi:10.1001/jamaoto.2021.0454

Corresponding Authors: Yi Ji, MD, PhD, Division of Oncology, Department of Pediatric Surgery (jijiyuanyuan@163.com), and Siyuan Chen, MD, PhD, Pediatric Intensive Care Unit, Department of Critical Care Medicine (siy_chen@163.com), West China Hospital of Sichuan University, 37# Guo-Xue-Xiang, Chengdu, 610041, China.

Author Contributions: Drs Ji and Chen had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Ji, Chen, Zhou, Jiang, Y. Zhang.

Acquisition, analysis, or interpretation of data: Ji, Yang, X. Zhang, Li, Xiang, T. Qiu, Dai, Lu, L. Qiu, Kong.

Drafting of the manuscript: Ji, Chen, Yang, X. Zhang, Zhou, T. Qiu, Dai, Jiang, Lu.

Critical revision of the manuscript for important intellectual content: Ji, Chen, Li, Xiang, L. Qiu, Kong, Y. Zhang.

Statistical analysis: Ji, Yang, X. Zhang, Zhou, T. Qiu, Dai, Jiang, Y. Zhang.

Obtained funding: Ji, Chen.

Administrative, technical, or material support: Ji, Li, Xiang, Lu, L. Qiu, Kong.

Supervision: Ji.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by grants 81400862 and 81401606 from the National Natural Science Foundation of China, grant 2019YFS0322 from the Key Project in the Science & Technology Program of Sichuan Province, grant 2015SU04A15 from the Science Foundation for The Excellent Youth Scholars of Sichuan University, and grants 2019HXFH056 and 2020XHFH048 from the 1·3·5 project for disciplines of excellence for the Clinical Research Incubation Project of West China Hospital of Sichuan University.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We acknowledge the support of all other involved investigators and participating practitioners, nurses, and residents for their valued contributions. We thank all of the patients and their parents and/or guardians who participated in this study. Additionally, we thank the parents of the patients who appear in images and are described in Supplement 2 for permission to publish this information. None of these individuals were compensated for their contributions.

Data Sharing Statement: See Supplement 3.

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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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