Infantile Hemangioma: Propranolol More Effective Than Corticosteroids?

Caroline Helwick

October 29, 2012

NEW ORLEANS — Propranolol might be more effective than corticosteroids for the treatment of infantile cutaneous hemangiomas, according to a systematic review and meta-analysis presented here at the Plastic Surgery 2012: American Society of Plastic Surgeons Annual Meeting.

"Propranolol was associated with greater efficacy than steroids after either systemic or local administration," reported Ali Izadpanah, MD, from McGill University in Montreal, Quebec, Canada.

Corticosteroids were also associated with double the rate of adverse effects, compared with propranolol, he added.

Infantile hemangioma is the most common benign vascular neoplasm of infancy, occurring in 1.0% to 2.5% of white infants, especially girls. Early intervention is indicated in a number of circumstances: visual field obstruction, respiratory obstruction, congestive heart failure, severe hemorrhage, and serious disfigurement.

Corticosteroids are considered first-line treatment, but recently, the beta blocker propranolol has been shown to be effective. Dr. Izadpanah explained that propranolol has 3 different molecular mechanisms of action: in the early phase, vasoconstriction; in the intermediate phase, inhibition of new angiogenesis; and in the delayed phase, induction of apoptosis.

"This is very different from corticosteroids, which are mainly anti-inflammatory," he said. "It is possible that the optimal approach will be to combine these 2 drugs. This is currently being studied."

Meta-analysis Conducted

To evaluate the effectiveness of corticosteroids and propranolol, Dr. Izadpanah and colleagues conducted a systematic review of reports published from 1946 to March 2012. Prospective, retrospective, and randomized controlled trials that reported adverse effects, duration of therapy, and success rates were included in the review. Studies that did not report outcomes or that included fewer than 10 cases were excluded.

Of the 1162 studies selected for inclusion, 16 assessed corticosteroids (n = 2629), 25 assessed propranolol (n = 795), and 3 assessed both. The majority (74%) were retrospective, but 3 (8%) were randomized controlled trials.

The most commonly used dose of corticosteroids was 2 to 3 mg/kg per day, and the typical duration of therapy was 4 to 12 weeks. In the corticosteroid-treated patients, the overall efficacy rate, compared with control subjects, was 69.1% (P < .0001).

The most commonly used dose of propranolol was 1 mg/kg per day, and the duration of therapy ranged from 4 weeks to 12 months. In the propranolol-treated patients, the overall efficacy rate, compared with control subjects, was 97.3% (P < .0001).

Adverse-Effect Profile

The most common adverse effects of corticosteroids, observed in 475 (17.6%) patients, were altered growth (6%), moon facies (5%), osteoporosis (2%), fungal injections (2%), and hypertension (2%).

The most common adverse effects of propranolol, observed in 77 (9.6%) patients were somnolence (2%), cold extremities (2%), diarrhea (2%), gastroesophageal reflux (2%), and fatigue (1%).

"We think propranolol could be superior as the first-line therapy for cutaneous hemangiomas," Dr. Izadpanah concluded.

He acknowledged that there were study limitations. The findings were based on retrospective studies that can have recall and reviewer bias, the power of the studies was small, and the studies offered limited details on extent of resolution and the use of additional therapies.

Some Surgeons Not Yet Convinced

The uptake of propranolol has increased in the year since the study was initiated, but some surgeons are still wary of it because of a concern for immediate adverse effects, Dr. Izadpanah told Medscape Medical News.

"There can be some hypotension and bradycardia, and this needs monitoring. This is different from corticosteroids, which have more long-term adverse effects, but [the adverse effects with propranolol] are not life-threatening," he noted.

Dr. Izadpanah suggested that patients undergo careful pretreatment screening to look for cardiac problems before being prescribed propranolol.

"Overall, I think the efficacy and cost-effectiveness will be greater with propranolol...but this needs to be shown in randomized controlled trials. These are being conducted now," he noted.

Session moderator Anand R. Kumar, MD, director of the facial skeletal surgery program at the Children's Hospital of Pittsburgh in Pennsylvania, commented on the findings.

"Corticosteroids have been shown to be effective in treating infantile hemangiomas, but nationally we are seeing more and more vascular anomaly centers using propranolol, including ours. We are clearly seeing a change in how we treat this complex problem, but the question now is what is the role for propranolol and what is its place with respect to corticosteroids," he said.

Dr. Kumar noted that conclusions cannot be based on a retrospective review, but the study "sets the stage for more cooperative comparison studies that will evaluate this." Future studies need to better define methods of assessing and defining efficacy, he added.

Dr. Izadpanah indicated that the new studies will strive to do that by, for example, using Doppler ultrasound to track disease regression, "so there will be outcome measurements beyond the clinical assessment."

Dr. Izadpanah and Dr. Kumar have disclosed no relevant financial relationships.

Plastic Surgery 2012: American Society of Plastic Surgeons (ASPS) Annual Meeting. Presented October 27, 2012.