Evaluating the Utility of Beta Blockers in Arteriovenous Malformations and Related Vascular Lesions: A Systematic Review

Arteriovenous malformations (AVMs) are high-flow vascular lesions formed by abnormal direct shunts between arteries and veins without an intervening capillary bed. They may present with swelling, pain, bleeding, ulceration, thrombosis, disfigurement, or, in advanced cases, high-output cardiac failure. Diagnosis is clinical and radiological, commonly requiring Doppler ultrasonography, computed tomography, magnetic resonance imaging or angiography depending on lesion site and flow characteristics.

Management of AVMs remains difficult because recurrence after incomplete treatment is common and because lesion behaviour varies by anatomical site, extent, haemodynamic profile and stage. Surgery combined with embolization remains the conventional approach when feasible, whereas systemic medical therapy is generally considered adjunctive. In contrast, propranolol and other beta-blockers have an established and reproducible role in infantile haemangioma (IH), where regression is attributed to vasoconstriction, down-regulation of angiogenic signalling and endothelial apoptosis. Whether those mechanisms translate meaningfully to true AVMs remains uncertain.

The literature on beta-blockers in AVMs is therefore clinically important but methodologically challenging. Published studies frequently mix true AVMs with IH, arteriovenous fistulas, dural malformations or other vascular anomalies and outcomes are measured inconsistently across imaging response, colour change, softening, symptom relief and need for reintervention. This heterogeneity can lead to overinterpretation if IH data are generalized to AVMs.

The present review was undertaken to synthesize the available evidence on beta-blocker therapy in AVMs and related vascular lesions, while explicitly separating AVM-specific findings from IH-dominant evidence wherever possible. The review focused on lesion response, symptom relief, adverse effects and the clinical position of beta-blockers as either primary or adjunctive therapy.

Study Design and Reporting Standard

This systematic review followed PRISMA 2020 reporting principles (Figure 1). Because the review protocol was not prospectively registered, this has been acknowledged as a limitation in the revised manuscript.

Review Question

The review question was: "What are the effects of beta-blockers in the treatment of arteriovenous malformations and related vascular lesions and how should AVM-specific findings be interpreted separately from IH-dominant evidence?"

Information Sources and Search Strategy

Studies published from January 2016 to October 2025 were searched in PubMed, Scopus and Web of Science. Additional records were sought through bibliography screening and Google Scholar. Search terms combined controlled vocabulary and keywords related to AVMs and related lesions ("arteriovenous malformation", "AVM", "haemangioma", "infantile haemangioma", "arteriovenous fistula", "vascular malformation", "dural malformation") with beta-blocker terms ("beta-blocker", "propranolol", "timolol", "atenolol", "metoprolol", "nadolol", "carteolol").

Eligibility Criteria

Eligibility was determined using PICOS. Population: patients of any age with AVMs or related vascular lesions evaluated in the included literature. Intervention: systemic or topical beta-blockers. Comparator: placebo, standard care, alternative therapy or no comparator in descriptive studies. Primary outcomes: lesion size/volume change, flow reduction or symptom improvement. Secondary outcomes: adverse events, requirement for surgery or embolization, recurrence/progression and functional outcomes. Randomized trials, non-randomized studies, retrospective studies, case series and case reports were eligible. Review articles, preclinical studies, abstracts without full data, duplicate publications and unpublished studies were excluded.

Study Selection and Data Extraction

Two reviewers independently screened titles, abstracts and full texts. Disagreements were resolved by discussion and, where required, consultation with an additional reviewer. Extracted variables included lesion type, anatomical site, age, sample size, concomitant therapy, beta-blocker type and dose, treatment duration, outcome measurement method, therapeutic response and adverse events.

Risk-of-Bias Assessment and Synthesis

The Joanna Briggs Institute (JBI) critical appraisal tools were used for cross-sectional studies and case reports and RoB 2 was used for randomized trials. Owing to the marked heterogeneity of lesion types, co-interventions, outcome definitions and follow-up durations, quantitative pooling was not considered appropriate; therefore, results were synthesized narratively, with emphasis on separating true AVM findings from IH-focused evidence.

The literature search identified 196 records from electronic databases and 6 additional records through manual searching. After removal of duplicates and screening, 18 studies met the inclusion criteria: 2 randomized controlled trials, 10 observational studies and 6 case reports.

The included evidence base was clinically mixed. A minority of reports focused on true AVMs, arteriovenous fistulas or cerebral proliferative angiopathy, whereas the majority addressed IH or mixed vascular anomaly cohorts. This scope mismatch is central to the interpretation of the review findings, because the strongest quantitative outcomes were derived from IH studies rather than AVM-specific studies.

Figure 1: PRISMA flow chart

Figure 2: Risk-of-bias figures retained from source

Table 1: Summary of AVM-specific versus IH-dominant findings

A total of 1750 patients were represented across the included studies. Most participants were infants, particularly in the IH literature, while AVM-specific reports included neonates, children and adults. Propranolol was the most frequently studied agent. Across studies, the usual starting oral dose ranged from 1 to 2 mg/kg/day, with treatment duration commonly spanning 5 to 12 months, although several AVM-focused reports used fixed doses or longer courses. Topical timolol, carteolol and 2% propranolol preparations were evaluated primarily in superficial IH cohorts.

AVM-specific outcomes were modest and inconsistent. Small case reports and retrospective series suggested possible symptom improvement, lesion softening, colour reduction, headache control, stabilization or partial radiological improvement in selected patients. However, the extracranial AVM series by Chastanet et al. reported no meaningful reduction in lesion volume despite some self-reported symptom benefit, supporting the interpretation that beta-blockers may stabilize or palliate symptoms rather than reliably shrink true AVMs.

IH-focused studies showed substantially stronger efficacy signals. The randomized trials and several observational studies demonstrated clinical response, lower complication rates in selected superficial lesions or non-inferiority of propranolol relative to steroids. These findings support established IH practice, but they should not be extrapolated directly to true AVMs.

Concomitant treatments were common, including steroids, furosemide, surgery, embolization, radiotherapy and migraine-directed medication. This reduces certainty about the isolated effect of beta-blockers in many AVM-focused reports. Safety events across the included literature included bradycardia, hypotension, wheeze/bronchospasm, gastrointestinal intolerance, hypoglycaemia and sleep or behavioural disturbance; topical agents were generally associated with fewer systemic adverse effects (Table 1).

Risk-of-bias assessment showed that both randomized trials had high risk of bias, primarily due to limitations in randomization and blinding. The observational and case-report literature provided useful descriptive information on dose, duration and adverse effects, but was inherently limited by small sample sizes, incomplete demographic reporting, confounding from co-interventions and non-standardized outcome assessment (Figure 1).

The principal finding of this review is that the apparent therapeutic promise of beta-blockers depends heavily on which lesion type is being considered. The most convincing evidence relates to IH, for which propranolol is already an accepted therapy. In contrast, the evidence base for true AVMs remains sparse, highly heterogeneous and dominated by case reports or small retrospective series.

This distinction is clinically important because IH and AVMs differ biologically and haemodynamically. Mechanisms proposed for propranolol in IH - including vasoconstriction, reduced angiogenic signalling and endothelial apoptosis - may not translate fully to high-flow AVMs. Accordingly, the reviewed AVM literature more commonly suggested symptom relief or lesion stabilization than consistent structural regression.

The review also highlights the interpretive challenge created by mixed vascular anomaly populations. Several included studies enrolled patients with haemangiomas, vascular malformations, fistulas or unspecified anomalies under a broad AVM-oriented search strategy. While this broad search was useful for capturing all potentially relevant beta-blocker experience, it also limited the certainty of AVM-specific conclusions and explains why a narrative synthesis was more appropriate than meta-analysis.

Another important observation is the frequent use of co-interventions. Beta-blockers were often administered alongside steroids, surgery, embolization, supportive heart-failure treatment or other medications. In such settings, therapeutic response cannot be attributed confidently to beta-blockade alone. Similarly, outcome measurement varied widely across studies, ranging from MRI-based lesion assessment to subjective cosmetic or symptomatic improvement.

From a practical standpoint, current evidence supports the established use of beta-blockers for IH and suggests that selected AVM patients may experience symptom benefit, short-term stabilization or improved tolerance of adjunctive treatment. However, current data do not justify routine use of beta-blockers as definitive stand-alone therapy for true AVMs. Careful counselling is needed so that changes in colour, softness or symptoms are not misinterpreted as durable cure.

The present review has strengths, including a structured PRISMA-based search, use of multiple databases, manual searching and formal risk-of-bias assessment. Its limitations include English-language restriction, probable publication bias toward positive case reports, inclusion of mixed lesion types, heterogeneity of outcomes, lack of protocol registration and the predominance of low-level evidence. These limitations should temper any clinical recommendation.

Future AVM-specific studies should use standardized lesion definitions, protocol registration, reproducible search reporting and uniform outcomes such as MRI-measured volume change, flow metrics, bleeding frequency, pain, need for reintervention and quality of life. Comparative work against other medical options, including targeted therapies, would also strengthen decision-making.

Beta-blockers remain strongly supported for infantile haemangioma, but evidence for true arteriovenous malformations is scarce and inconsistent. In selected AVM cases, propranolol or related agents may provide symptomatic relief or short-term stabilization, yet they do not currently demonstrate reliable AVM volume reduction across the limited published literature. Until better AVM-specific trials become available, beta-blockers should be regarded as adjunctive or exploratory therapy rather than definitive primary treatment for AVMs.

Strengths and Limitations

Strengths include transparent study identification, use of multiple databases, manual searching and formal bias assessment.

The main limitations are lesion-type heterogeneity, English-only inclusion, frequent co-interventions, non-standardized outcomes and the predominance of low-level evidence for true AVMs.

Implications for Practice

Beta-blockers should continue to be interpreted as standard therapy for IH, not as established curative therapy for AVMs.

For selected AVM patients, a monitored trial of beta-blocker therapy may be considered for symptom control or short-term stabilization, with explicit counselling regarding uncertainty, follow-up imaging and stopping rules if there is no response or if adverse effects occur.

Data Availability

The review was based on published studies. The study-selection decisions, extracted variables and bias assessments are available from the corresponding author upon reasonable request.

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Appendix Table 1: Retained source table