Topical Propranolol Improves Epistaxis Control in Hereditary Hemorrhagic Telangiectasia (HHT): A Randomized Double-Blind Placebo-Controlled Trial

Abstract

Epistaxis is a common debilitating manifestation in hereditary hemorrhagic telangiectasia (HHT), due to mucocutaneous telangiectases. The epistaxis can be difficult to control despite available treatments. Dysregulated angiogenesis has been shown to be associated with telangiectases formation. Topical propranolol has demonstrated antiangiogenic properties. We performed a two-phase study, i.e., a double-blind placebo-controlled phase, followed by an open-label phase. The aim of the study was assessment of safety and efficacy of nasal propranolol gel in HHT-related epistaxis. Twenty participants with moderate-severe HHT-related epistaxis were randomized to eight weeks of propranolol gel 1.5%, or placebo 0.5 cc, applied to each nostril twice daily; and continued propranolol for eight weeks in an open-label study. For the propranolol group, the epistaxis severity score (ESS) improved significantly (−2.03 ± 1.7 as compared with −0.35 ± 0.68 for the placebo group, p = 0.009); hemoglobin levels improved significantly (10.5 ± 2.6 to 11.4 ± 2.02 g/dL, p = 0.009); and intravenous iron and blood transfusion requirement decreased. The change in nasal endoscopy findings was not significant. During the open-label period, the ESS score improved significantly in the former placebo group (−1.99 ± 1.41, p = 0.005). The most common adverse event was nasal mucosa burning sensation. No cardiovascular events were reported. Our results suggest that topical propranolol gel is safe and effective in HHT-related epistaxis.

The Use of Beta-Blockers in Hereditary Hemorrhagic Telangiectasia-Related Epistaxis: A Systematic Review

“…One hundred and fifteen studies were excluded because they did not meet the inclusion criteria, resulting in 5 articles to be included (2 case series and 3 randomized control trials [RCT]), totaling 132 patients (Table 1). [9][10][11][12][13] Three studies evaluated propranolol and 2 assessed timolol. In the 3 RCTs, 29 participants received topical timolol as a spray, 11 10 received topical propranolol as a gel 12 and 14 received topical timolol as a gel, 13 respectively.…”

“…Mei-Zahav et al found a significant improvement in both their case series (9.4 ± 3.1 to 11 ± 1.8 g/dL, P = .043) 10 and RCT (10.5 ± 2.6 to 11.4 ± 2.02 g/dL, P < .001). 12 Both studies assessed propranolol gel. Peterson et al and Dupuis-Girod et al both used timolol (gel and spray, respectively), and neither demonstrated a statistically significant difference in hemoglobin levels between study groups.…”

The Role of Propranolol as a Repurposed Drug in Rare Vascular Diseases

“…The severity of epistaxis and the number of blood transfusions pre-and post-administration were reduced rapidly and significantly [39]. As continuation of this study, the same group successfully finished a recent double-blind placebo-controlled study to assess the efficacy and safety of topical propranolol for moderate-severe epistaxis in 24 HHT patients [40].…”

Hereditary Hemorrhagic Telangiectasia Associating Neuropsychiatric Manifestations with a Significant Impact on Disease Management—Case Report and Literature Review

“…Patient support groups/patient associations are proven to be very effective in helping all rare disease patients, in general, to better cope with their illness; unfortunately, in our case, the patient did not agree to be referred to a rare disease organization and no specific HHT patient group was locally available. The current guidelines for the approach to HHT [ 10 , 63 ] and research evidence show a broadening spectrum of therapeutic solutions like well-known or repurposed drugs (including bevacizumab, propranolol, pazopanib, tacrolimus, and antithrombotic drugs) and new surgical techniques [ 64 , 65 , 66 , 67 , 68 , 69 ]. These would require more supporting evidence on efficacy and standardized algorithms for clinical use.…”