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.
BACKGROUND: Infantile hemangioma (IH) is the most common benign vascular tumor of infancy. Propranolol is considered first-line therapy for IH. However, it is associated with side effects. Therefore, there was a need for alternative therapy. Atenolol, a selective b1-blocker may be free from such side effects. Hence, the present study aims to develop a more accurate estimate of the safety and efficacy of atenolol compared to propranolol in the treatment of IH.
METHODOLOGY: A search of various literature databases (PubMed, Embase, Ovid, Scopus, Cochrane Central, CINAHL, Web of Science, and Google Scholar) was done to identify studies which compared propranolol versus atenolol in the treatment of IH. The combined odds ratio along with corresponding 95% confidence intervals (CIs) were evaluated using a fixed-effects model.
RESULTS: A total of 300 articles were screened of which five studies including 116 patients in atenolol arm and 138 patients in the propranolol arm were analyzed. Atenolol was comparable to propranolol in terms of efficacy as no significant difference was seen between both the treatment arms in terms of hemangioma activity score (mean difference 0.25 [95% CI;‒0.21, 0.71]) and complete response (odds ratio [OR] =0.43; 95% CI; 0.17, 1.11; P = 0.08,). Atenolol therapy was better than propranolol in terms of safety, i.e., serious/potentially serious side effect, (OR = 0.11; 95% CI; 0.02, 0.51; P = 0.005) and wheezing/bronchial hyperreactivity (OR = 0.11; 95% CI; 0.02, 0.51; P = 0.005).
CONCLUSION: The present meta-analysis provides evidence that atenolol has got a comparable efficacy and better safety profile with propranolol.
Background: Infantile hemangioma (IH) is common in children, which may bring about cosmetically disfiguring, functional impairment, and exhibiting complications. There had been various therapies and we aimed to assess the efficacy and adverse effects of different therapies through network meta-analysis. Methods: We searched PubMed, Embase, Cochrane Library and Web of Science (from database inception to April 11, 2020) for studies assessing the efficacy, success rate and adverse effects. Direct pairwise comparison and a network meta-analysis under random effects were performed. We also assessed the ranking probability. Findings: A total of 30 randomized clinical trials with more than 20 different therapeutic regimens were identified. Treatment combined propranolol orally with laser could improve the curative effect than monotherapy. Laser with topical β blockers showed more efficiency than others whether in children under 6 months or not. The long-pulsed dye laser might be the best laser therapy. A higher dose and a longer treatment duration of propranolol orally achieved a higher success rate and increased side effects. Plus pulse dye laser with propranolol had the lowest incidence of adverse reactions, such as ulcer, color sink and color reduction. Interpretation: A combination of β blockers and laser might be the first-line treatment of IHs and a longer pulsed dye laser is preferred. Funding: No funding was received.
Infantile haemangioma (IH) is a benign vascular tumour type that occurs in 3 10% of infants. In the present meta analysis, previous studies comparing clinical outcomes, including the recovery rate and haemangioma activity score (HAS), adverse effects and relapse rates, were compared between patients treated with atenolol and those treated with propranolol for IH. A systematic search in various databases, including Medline, Cochrane Controlled Register of Trials, ScienceDirect and Google Scholar from inception until July 2019 was performed. The Cochrane risk of bias tool was used to assess the quality of published trials. A meta analysis with a random effects model and reported pooled mean differences (MD) or odds ratios (OR) with 95% CIs was performed. In total, 8 studies including 608 participants were analyzed. Only 2 studies were randomized controlled trials, while the majority of studies had low or unclear bias risks. Except for the response to medication (pooled OR=1.49; 95% CI, 0.85 2.18), all other outcomes (HAS, adverse reactions and relapse rate) were better for the atenolol group than the propranolol group. Atenolol resulted in better HAS (pooled MD=0.16; 95% CI, 0.42 to 0.73). Propranolol had more adverse reactions (pooled OR=2.17; 95% CI, 0.93 5.06) and a higher relapse rate (pooled OR, 1.67; 95% CI, 0.44 6.41) when compared to atenolol. However, these findings were not statistically significant. The results of this analysis suggest that atenolol may be non inferior to propranolol and may offer advantages, including lower adverse reactions and relapse rates.
Recently, several studies have reported their experience in using oral atenolol in patients with infantile haemangioma (IH), especially as an alternative to propranolol, but the efficacy and safety of oral atenolol has not been evaluated. We searched PubMed (Medline), Central, Embase, Web of Science and EBSCOhost (until May 2018) for the eligible studies reporting more than 10 IH patients who were treated with oral atenolol with detailed original data, including outcomes, regimens and adverse events (AEs). The data was standardised and analysed by using R software with meta-package. A total of 9 of 141 identified articles, including 341 infantile haemangioma patients treated with oral atenolol therapy, were included. The pooled response rate of atenolol was 0.90 (95% CI: 0.85-0.93), and the rebound rate was 0.11 (95% CI: 0.08-0.16). Among the 341 patients, 44 patients were switched to atenolol therapy from propranolol due to adverse events. The response rate of subsequent atenolol treatment was 90.9% (40/44). Regarding AEs, 141 patients reported 177 episodes of AEs, and the pooled rate was 0.26 (95% CI: 0.12-0.47). Gastrointestinal symptoms (e.g. constipation, diarrhoea and vomiting) were the most frequent AEs (22.6%). Widely known propranolol-related AEs, including hypoglycaemia, bronchospasm, bradycardia and hypotension, were not recorded. Overall, atenolol appears to be an effective and safe therapy for the treatment of IH and may be a promising alternative to propranolol.
Background: Infantile haemangiomas (previously known as strawberry birthmarks) are soft, raised swellings of the skin that occur in 3% to 10% of infants. These benign vascular tumours are usually uncomplicated and tend to regress spontaneously. However, when haemangiomas occur in high-risk areas, such as near the eyes, throat, or nose, impairing their function, or when complications develop, intervention may be necessary. This is an update of a Cochrane Review first published in 2011. Objectives: To assess the effects of interventions for the management of infantile haemangiomas in children. Search methods: We updated our searches of the following databases to February 2017: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, LILACS, and CINAHL. We also searched five trials registries and checked the reference lists of included studies for further references to relevant trials. Selection criteria: Randomised controlled trials (RCTs) of all types of interventions, versus placebo, active monitoring, or other interventions, in any child with single or multiple infantile haemangiomas (IHs) located on the skin. Data collection and analysis: We used standard methodological procedures expected by Cochrane. The primary outcome measures were clearance, a subjective measure of improvement, and adverse events. Secondary outcomes were other measures of resolution; proportion of parents or children who consider there is still a problem; aesthetic appearance; and requirement for surgical correction. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. Main results: We included 28 RCTs, with a total of 1728 participants, assessing 12 different interventions, including lasers, beta blockers (e.g. propranolol, timolol maleate), radiation therapy, and steroids. Comparators included placebo, an active monitoring approach, sham radiation, and interventions given alone or in combination. Studies were conducted in a number of countries, including China, Egypt, France, and Australia. Participant age ranged from 12 weeks to 13.4 years. Most studies (23/28) included a majority of females and different types of IHs. Duration of follow-up ranged from 7 days to 72 months. We considered most of the trials as at low risk of random sequence generation, attrition bias, and selective reporting bias. Domains such as allocation concealment and blinding were not clearly reported in general. We downgraded evidence for issues related to risk of bias and imprecision. We report results for the three most important comparisons, which we chose on the basis of current use. Outcome measurement of these comparisons was at 24 weeks' follow-up. Oral propranolol versus placebo Compared with placebo, oral propranolol 3 mg/kg/day probably improves clinician-assessed clearance (risk ratio (RR) 16.61, 95% confidence interval (CI) 4.22 to 65.34; 1 study; 156 children; moderate-quality evidence) and probably leads to a clinician-assessed reduction in mean haemangioma volume of 45.9% (95% CI 11.60 to 80.20; 1 study; 40 children; moderate-quality evidence). We found no evidence of a difference in terms of short- or long-term serious adverse events (RR 1.05, 95% CI 0.33 to 3.39; 3 studies; 509 children; low-quality evidence), nor in terms of bronchospasm, hypoglycaemia, or serious cardiovascular adverse events. The results relating to clearance and resolution for this comparison were based on one industry-sponsored study. Topical timolol maleate versus placebo The chance of reduction of redness, as a measure of clinician-assessed resolution, may be improved with topical timolol maleate 0.5% gel applied twice daily when compared with placebo (RR 8.11, 95% CI 1.09 to 60.09; 1 study; 41 children;low-quality evidence). Regarding short- or long-term serious cardiovascular events, we found no instances of bradycardia (slower than normal heart rate) or hypotension in either group (1 study; 41 children; low-quality evidence). No other safety data were assessed, and clearance was not measured. Oral propranolol versus topical timolol maleate When topical timolol maleate (0.5% eye drops applied twice daily) was compared with oral propranolol (via a tablet taken once per day, at a 1.0 mg/kg dose), there was no evidence of a difference in haemangioma size (as a measure of resolution) when measured by the proportion of patients with a clinician-assessed reduction of 50% or greater (RR 1.13, 95% CI 0.64 to 1.97; 1 study; 26 participants; low-quality evidence). Although there were more short- or long-term general adverse effects (such as severe diarrhoea, lethargy, and loss of appetite) in the oral propranolol group, there was no evidence of a difference between groups (RR 7.00, 95% CI 0.40 to 123.35; 1 study; 26 participants; very low-quality evidence). This comparison did not measure clearance. None of our key comparisons evaluated, at any follow-up, a subjective measure of improvement assessed by the parent or child; proportion of parents or children who consider there is still a problem; or physician-, child-, or parent-assessed aesthetic appearance. Authors' conclusions: We found there to be a limited evidence base for the treatment of infantile haemangiomas: a large number of interventions and outcomes have not been assessed in RCTs. Our key results indicate that in the management of IH in children, oral propranolol and topical timolol maleate are more beneficial than placebo in terms of clearance or other measures of resolution, or both, without an increase in harms. We found no evidence of a difference between oral propranolol and topical timolol maleate with regard to reducing haemangioma size, but we are uncertain if there is a difference in safety. Oral propranolol is currently the standard treatment for this condition, and our review has not found evidence to challenge this. However, these results are based on moderate- to very low-quality evidence. The included studies were limited by small sample sizes and risk of bias in some domains. Future trials should blind personnel and participants; describe trials thoroughly in publications; and recruit a sufficient number of children to deduce meaningful results. Future trials should assess patient-reported outcomes, as well as objective outcomes of benefit, and should report adverse events comprehensively. Propranolol and timolol maleate require further assessment in RCTs of all types of IH, including those considered problematic, as do other lesser-used interventions and new interventions. All treatments should be compared against propranolol and timolol maleate, as beta blockers are approved as standard care.
Antecedentes: Los cursos largos de corticosteroides orales se usan comúnmente en niños en el manejo de condiciones crónicas. Se sabe que se producen varias reacciones adversas a los medicamentos (ADR) con su uso. Esta revisión sistemática tuvo como objetivo identificar las ADR más comunes y graves y determinar sus niveles de riesgo relativo. Se realizó una búsqueda bibliográfica de Embase, Medline, International Pharmaceutical Abstracts, CINAHL, Biblioteca Cochrane y PubMed sin restricciones de lenguaje para identificar estudios en los que se administraron corticosteroides orales a pacientes de 28 días a 18 años de edad por lo menos 15 Días de tratamiento. Cada base de datos se realizó una búsqueda desde sus fechas más tempranas hasta enero de 2016. Todos los estudios que proporcionaron información clara sobre ADRs fueron incluidos. RESULTADOS: Cien y un estudios que incluyeron 33 estudios prospectivos de cohortes; 21 ensayos controlados aleatorios; 21 series de casos y 26 informes de casos cumplieron los criterios de inclusión. Éstos involucraron a 6817 niños y reportaron 4321 ADRs. Los tres ADR experimentados por el mayor número de pacientes fueron el aumento de peso, el retraso del crecimiento y características de Cushingoid con las tasas de incidencia respectivas de 21,1%, 18,1% y 19,4% de los pacientes evaluados para estas ADR. 21,5% de los pacientes medidos mostraron disminución de la densidad ósea y 0,8% de los pacientes mostraron osteoporosis. La supresión bioquímica del eje HPA se detectó en 269 de 487 pacientes en los que se midió. La infección fue la ADR más grave, con veintiuna muertes. El varicela zóster fue la infección más frecuente (9 muertes). CONCLUSIONES: El aumento de peso, el retraso del crecimiento y las características de Cushingoid fueron las ADR más frecuentes observadas cuando se administraron corticosteroides orales a largo plazo a los niños. La mayor susceptibilidad a la infección fue la ADR más grave.
CONTEXTO: Los hemangiomas infantiles (IH) pueden estar asociados con un impacto funcional significativo. OBJETIVO: El objetivo de este estudio fue el de realizar un metanálisis de estudios de intervenciones farmacológicas en niños con IH. FUENTES DE DATOS: Las fuentes de datos fueron Medline y otras bases de datos de 1982 a junio de 2015. SELECCIÓN DEL ESTUDIO: Dos revisores evaluaron los estudios usando criterios de inclusión predeterminados. EXTRACCIÓN DE DATOS: Un revisor extrajo los datos con una revisión por un segundo. RESULTADOS: Se incluyeron 18 estudios en un meta-análisis de red evaluando las tasas relativas esperadas de aclaramiento de IH asociado con β-bloqueantes y esteroides. El propranolol oral tuvo la mayor estimación media de aclaramiento esperado (95% IC 95%: 88% -99%) en comparación con corticosteroides orales (43%, 95% BCI: 21% -66%) y control 6%, 95% BCI: 1% -11%). La fuerza de la evidencia (SOE) fue alta para los efectos del propranolol sobre la reducción del tamaño de la lesión en comparación con la observación / placebo. Los corticoesteroides demostraron una efectividad moderada al reducir el tamaño / volumen (SOE moderada para mejorar en IH). SOE fue baja para los efectos de timolol tópico versus placebo. LIMITACIONES: Las limitaciones metodológicas de la evidencia disponible pueden comprometer la SOE. La validez de las estimaciones meta-analíticas se basa en la suposición de intercambiabilidad entre los estudios, condicionada a los efectos de la intervención. Los resultados dependen de la supuesta falta de sesgo de información. Conclusiones: El propranolol es eficaz para reducir el tamaño de IH en comparación con el placebo, la observación y otros tratamientos, incluidos los esteroides, en la mayoría de los estudios. Los corticosteroides demuestran una efectividad moderada en la reducción del tamaño / volumen de IH. Los cálculos de metanálisis proporcionan una clasificación relativa de las tasas anticipadas de eliminación de lesiones entre los tratamientos. Las familias y los médicos que toman decisiones de tratamiento también deben tener en cuenta factores como el tamaño de la lesión, la ubicación, el número y el tipo, y las preferencias del paciente y de la familia.
ANTECEDENTES: Los estudios epidemiológicos que evaluaron los tratamientos para hemangiomas infantiles han producido resultados inconsistentes. Se realizó un metanálisis de los datos publicados para investigar la efectividad y seguridad del propranolol oral versus otros tratamientos para hemangiomas infantiles. Métodos: Se realizó un metanálisis basado en la literatura (publicada desde 1960 hasta el 1 de diciembre de 2014) que se encuentra en los motores de búsqueda PubMed, EMBASE y OVID. Para las medidas de resultado se estimaron las odds ratios (OR) agrupadas y los intervalos de confianza del 95% (IC). Se realizaron heterogeneidad, sesgo de publicación y análisis de subgrupos. RESULTADOS: Un total de 61 estudios con 5.130 participantes cumplieron con los criterios de inclusión. Se encontró que el propranolol era una modalidad más eficaz en el tratamiento de las IH (OR = 0,92; IC del 95%: 0,89-0,95) y presentó menos complicaciones que los otros tratamientos, incluyendo los esteroides sistémicos (OR = 0,68; IC del 95%: 0,59-0,76) ; Ablación con láser (OR = 0,55; IC del 95%, 0,43 - 0,67); Otros bloqueadores beta-adrenérgicos (OR = 0,56; IC del 95%: 0,50-0,61) y cirugía (OR = 0,55; IC del 95%: 0,28-0,81). Un análisis de subgrupos de propranolol mostró que una dosis de 2 mg / kg / día o más arrojó mejores resultados (OR = 0,92, IC del 95%, 0,88-0,95, OR = 0,95, IC del 95%, 0,89-1,00) e IHs que No habían sido tratadas previamente tuvieron mejores respuestas al tratamiento con propranolol (OR = 0,95, IC del 95%, 0,91-0,98). CONCLUSIONES: El metanálisis demostró que el propranolol era más eficaz y más seguro que otras terapias en el tratamiento de IH. Proporciona una fuerte evidencia para apoyar el uso de propranolol como una terapia de primera línea para IHs.
ANTECEDENTES: El propranolol puede ha mostrado excelentes resultados como una terapia de primera línea en los hemangiomas infantiles (IHS) de todos los sitios del cuerpo, pero esta conclusión sigue siendo controvertido. En un intento de resolver este problema, se realizó un meta-análisis.
MÉTODOS: Una búsqueda de la literatura por PubMed, MEDLINE, Cochrane Library bases de datos y China Infraestructura Nacional del Conocimiento (CNKI) se realizó para identificar los estudios que estiman la eficacia del tratamiento con propranolol en lactantes con hemangiomas todos los sitios del cuerpo. Se evaluó el odds-ratio (OR) con los intervalos de confianza del 95% (IC) mediante un modelo de efectos fijos.
RESULTADOS: Treinta y cinco estudios con 324 pacientes hemangiomas infantiles (HI) y 248 controles fueron recuperados y analizados. La eficacia de propranolol es más de otras terapias en el tratamiento de IHs (OR = 9,67, IC :6.62-14 95% 0.12, P <0.001).En el análisis estratificado por sitios de tumor, propranolol es un tratamiento más eficaz en comparación con los esteroides (OR = 9,67, IC 95% :6.61-14 .15, P <0,001), vincristina (OR = 9,00, IC :2.15-37 0,66 95%, P = 0,003) y láser (OR = 9,00, IC :1.42-57 95% 0,12, P = 0,020) en el tratamiento de IHs cutáneas (OR = 24,95, IC :9.48-65 95% 0,64, P <0,001), periocular IHs (OR = 9,39, IC :3.88-22 0,71 95%, P <0,001), hemangiomas infantiles vías respiratorias (OR = 20,91, IC95 :7.81-55 .96%, P <0,001) y hemangiomas hepáticos infantiles (OR = 9,89, IC 95%: 1.20- 81,54, P = 0,033).
En conclusión, en los aspectos de la eficacia, el meta-análisis actual proporciona una fuerte evidencia de propranolol como tratamiento de primera línea para los hemangiomas infantiles.
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.
